Affinage

VGF

Neurosecretory protein VGF · UniProt O15240

Length
615 aa
Mass
67.3 kDa
Annotated
2026-04-28
100 papers in source corpus 37 papers cited in narrative 37 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

VGF is a neurotrophin- and activity-regulated secreted neuropeptide precursor that is proteolytically processed by prohormone convertases PC1/3 and PC2 into bioactive C-terminal peptides (TLQP-21, TLQP-62, AQEE-30, LQEQ-19, NERPs) released from large dense core vesicles via the regulated secretory pathway (PMID:7595538, PMID:12065665, PMID:16221685). Transcription of VGF is controlled by a CREB/CRE-dependent promoter element cooperating with Ras/NGFI-A and neuron-specific bHLH (MASH1/HEB-p300) complexes, while its translation is regulated post-transcriptionally through an mTOR-dependent mechanism repressed by the 3′UTR (PMID:1377233, PMID:8756618, PMID:11755530, PMID:34238925). VGF-derived peptides signal through the G protein-coupled receptor C3aR1 and the receptor gC1qR/C1qBP to modulate energy homeostasis via sympathoadrenal activation of adipose tissue, hippocampal synaptic plasticity and memory consolidation through a BDNF-TrkB positive feedback loop, microglial phagocytosis and motility, spinal nociceptive signaling via p38 MAPK in microglia, and insulin granule biogenesis and glucose-stimulated insulin secretion in pancreatic beta cells (PMID:23940034, PMID:24106277, PMID:10433265, PMID:18815270, PMID:22768837, PMID:28877479, PMID:19846725, PMID:31924226). VGF additionally promotes oligodendrogenesis, neural progenitor proliferation, and exerts brain region-specific antidepressant or pro-depressant effects—with ketamine's antidepressant action requiring VGF expression and AMPA receptor/mTOR signaling downstream of TLQP-62 (PMID:27732860, PMID:24747217, PMID:29158577, PMID:30504797).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1989 High

    Before VGF's molecular function was known, ultrastructural co-localization with vasopressin and oxytocin in hypothalamic neurosecretory terminals established it as a candidate secreted neuropeptide rather than an intracellular signaling protein.

    Evidence Immunocytochemistry with two antisera plus electron microscopy in rat hypothalamus

    PMID:2556505

    Open questions at the time
    • No identification of processed peptides
    • Secretion stimulus not tested
    • Function of VGF in these neurons unknown
  2. 1992 High

    Defining how neurotrophin signals reach the VGF locus, studies showed that a CRE immediately upstream of the transcription start site is both necessary and sufficient for NGF/cAMP-mediated induction, with CREB binding this element—establishing VGF as a direct CREB target gene.

    Evidence Promoter mutagenesis, EMSA for CREB binding, and transcription reporter assays in PC12 cells

    PMID:1377233 PMID:1570299 PMID:2017159

    Open questions at the time
    • Chromatin-level regulation not addressed
    • In vivo relevance of CRE not tested
  3. 1996 High

    The question of how multiple cis-elements cooperate was resolved by showing that NGF-induced VGF transcription requires three elements—CRE, CCAAT, and a G(S)G element binding the Ras-induced factor NGFI-A—none sufficient alone, placing VGF downstream of the Ras-MAPK cascade.

    Evidence Chimeric reporter mutagenesis, dominant-negative Ras, TrkA mutants, EMSA in PC12 cells

    PMID:8756618

    Open questions at the time
    • Relative contribution of each element in vivo undetermined
    • Post-translational modifications of NGFI-A at VGF promoter not characterized
  4. 1997 High

    Cell-type restriction of VGF expression was explained by the finding that the E-box/CCAAT region recruits a repressive HEB complex in non-neuronal cells but a stimulatory MASH1-p300 complex in neuronal cells, later shown to involve CREB-p300 cooperation for neurotrophin-dependent activation.

    Evidence EMSA, expression cloning, reporter mutagenesis, co-immunoprecipitation, and ChIP

    PMID:11755530 PMID:9032251

    Open questions at the time
    • Epigenetic marks distinguishing repressor vs. activator states not mapped
    • In vivo ChIP not performed
  5. 1995 High

    The question of whether VGF is a regulated secretory molecule was answered: VGF precursor undergoes tissue-specific post-ER cleavage into low-MW peptides enriched in secretory vesicles and preferentially released upon depolarization, confirming regulated dense-core vesicle secretion.

    Evidence Subcellular fractionation, immunoblotting with domain-specific antisera, depolarization-induced secretion in cerebellar granule and PC12 cells

    PMID:7595538

    Open questions at the time
    • Convertases responsible not yet identified
    • Sorting signals not mapped
  6. 2002 High

    The identity of VGF-processing enzymes was established: PC1/3 and PC2 cleave VGF at KRKRKK(488) and RPR(555) to generate the major C-terminal fragments VGF20 and VGF10, and novel brain peptides were structurally identified by mass spectrometry.

    Evidence Ectopic PC1/3 and PC2 expression in GH3 cells, site-directed mutagenesis, MALDI-ToF MS and Edman degradation of rat brain extracts

    PMID:12065665

    Open questions at the time
    • Full peptidomic catalogue of VGF-derived peptides incomplete
    • Tissue-specific differences in processing not fully mapped
  7. 2005 High

    The sorting mechanism was resolved: a C-terminal alpha-helix containing the 564RRR566 convertase site and adjacent 567HFHH570 residues are required for VGF entry into the regulated secretory pathway, linking prohormone processing to vesicular trafficking.

    Evidence Systematic mutagenesis, confocal imaging, subcellular fractionation, PC inhibitor in PC12 and INS-1 cells

    PMID:16221685

    Open questions at the time
    • Chaperone or adaptor mediating recognition of this signal unknown
    • Whether this mechanism generalizes to all tissues not tested
  8. 1999 High

    The first physiological role was established: VGF knockout mice are lean, hypermetabolic, hyperactive, and infertile, demonstrating a non-redundant requirement for VGF in energy homeostasis and reproduction.

    Evidence Germline VGF KO mice, metabolic phenotyping, in situ hybridization for hypothalamic neuropeptides

    PMID:10433265

    Open questions at the time
    • Which VGF-derived peptide(s) mediate the metabolic phenotype unknown
    • CNS vs. peripheral contributions not separated
  9. 2002 High

    VGF was placed in the melanocortin pathway: genetic epistasis showed VGF deficiency blocks obesity in agouti (Ay/a) mice but only attenuates it in ob/ob mice, positioning VGF downstream of MC4R signaling in autonomic outflow circuits.

    Evidence Double-mutant crosses (VGF KO × Ay/a, ob/ob, db/db), in situ hybridization, leptin injection

    PMID:12177191

    Open questions at the time
    • Direct MC4R-to-VGF transcriptional mechanism not shown
    • Peripheral VGF contributions not excluded
  10. 2006 High

    The first bioactive VGF peptide was functionally characterized: ICV TLQP-21 increases energy expenditure and prevents diet-induced obesity by stimulating sympathoadrenal activation of brown and white adipose tissue, independent of thyroid hormones.

    Evidence LC-MS/MS peptide identification from brain, chronic ICV infusion, indirect calorimetry, adipose gene expression, hormonal measurements in mice

    PMID:16983076

    Open questions at the time
    • Receptor for TLQP-21 not yet identified
    • Direct vs. indirect sympathetic activation not distinguished
  11. 2008 High

    TLQP-62 was shown to modulate hippocampal synaptic plasticity: it induces transient potentiation through a BDNF-TrkB-dependent mechanism (blocked by TrkB-Fc and tPA inhibition), and VGF KO mice lack hippocampal LTD and have impaired spatial learning and fear memory.

    Evidence Electrophysiology in hippocampal slices, pharmacological blockade, VGF KO behavioral testing

    PMID:18815270

    Open questions at the time
    • Direct receptor for TLQP-62 not identified
    • Whether TLQP-62 acts pre- or post-synaptically unknown
  12. 2009 High

    VGF peptides were linked to pain signaling: AQEE-30 and LQEQ-19 evoke thermal hyperalgesia via p38 MAPK activation specifically in spinal microglia, and VGF is upregulated in DRG neurons after nerve injury, establishing VGF as a pro-nociceptive mediator.

    Evidence Intrathecal peptide injection, thermal assays, p38 immunostaining in spinal cord, DRG proteomics

    PMID:19846725

    Open questions at the time
    • Receptor mediating spinal microglial activation not identified
    • Whether VGF peptides act as neuron-to-microglia signals in vivo not proven
  13. 2013 High

    Two receptors for TLQP-21 were identified: C3aR1 (a GPCR with Gi/o coupling) deorphanized by unbiased RNA-seq screening, and gC1qR/C1qBP identified by chemical cross-linking/MS, establishing the first direct receptor-ligand relationships for VGF-derived peptides.

    Evidence Genome-wide RNA-seq deorphanization, siRNA knockdown, chemical cross-linking/MS, receptor antagonists, Ca2+ imaging, macrophage migration, and in vivo pain models

    PMID:23940034 PMID:24106277

    Open questions at the time
    • Relative contribution of C3aR1 vs. gC1qR in different tissues not systematically compared
    • Structural basis of TLQP-21 binding to either receptor unknown
  14. 2014 High

    VGF was shown to be a granin that drives dense-core vesicle biogenesis: VGF KO adrenal chromaffin cells have smaller LDCVs, while VGF expression in fibroblasts generates LDCV-like structures with regulated secretion, and humanized knock-in alleles rescue the hypertensive phenotype.

    Evidence VGF KO and humanized knock-in mice, electron microscopy, catecholamine measurements, blood pressure telemetry, VGF overexpression in NIH 3T3 cells

    PMID:24497580

    Open questions at the time
    • Mechanism by which VGF nucleates granule formation not elucidated
    • Contribution of individual VGF peptides vs. full-length protein to granule biogenesis not separated
  15. 2014 High

    Endogenous TLQP-21 was validated as a spinal pain mediator: immunoneutralization with intrathecal anti-TLQP-21 antibody blocked tactile and thermal hypersensitivity in both inflammatory and neuropathic pain models, acting through p38 and COX/LOX pathways.

    Evidence Intrathecal antibody administration, von Frey and thermal assays, pharmacological inhibitors in CFA and spared nerve injury models

    PMID:24657450

    Open questions at the time
    • Specific receptor(s) mediating spinal TLQP-21 pro-nociceptive effect not definitively assigned
    • Cell-type-specific contribution (microglia vs. neurons) in spinal cord not fully resolved
  16. 2015 High

    A VGF-BDNF positive feedback loop for memory was established: fear training induces hippocampal TLQP-62 secretion, which activates TrkB and CREB; sequestering TLQP-62 after training impairs memory, and BDNF rescue restores it, placing VGF upstream and downstream of BDNF signaling.

    Evidence In vivo fear conditioning, intra-hippocampal antibody infusion, TrkB phosphorylation in slices, VGF KO and BDNF rescue, Rac1/cofilin/synapsin pathway analysis

    PMID:26180209

    Open questions at the time
    • Direct receptor for TLQP-62 still unidentified
    • How TLQP-62 triggers BDNF release mechanistically unknown
  17. 2017 High

    VGF was shown to be essential for insulin secretory granule biogenesis: beta-cell-specific VGF KO profoundly impairs stimulus-coupled insulin secretion by disrupting cargo exit from the trans-Golgi network, proinsulin processing, and granule replenishment.

    Evidence Conditional KO (floxed VGF × beta-cell Cre), islet secretion assays, electron microscopy, TGN trafficking analysis

    PMID:28877479

    Open questions at the time
    • Molecular partners mediating VGF's role at TGN not identified
    • Whether VGF's granin function vs. its peptide products drive granule biogenesis not resolved
  18. 2017 High

    Region-specific roles of VGF in mood regulation were mapped: dorsal hippocampal VGF is antidepressant while nucleus accumbens VGF is pro-depressant; ketamine's antidepressant action requires VGF and signals through AMPA receptors and mTOR downstream of TLQP-62.

    Evidence AAV-Cre regional KO/overexpression in floxed VGF mice, social defeat and forced swim tests, rapamycin and NBQX pharmacology

    PMID:29158577

    Open questions at the time
    • Cell-type identity of VGF neurons mediating antidepressant vs. pro-depressant effects not fully resolved
    • Whether TLQP-62 is the sole mediator in each region not established
  19. 2020 High

    TLQP-21's microglial actions were dissected across two receptors: C3aR1 mediates phagocytosis and chemotaxis (validated by C3aR1-KO transcriptomics), while C1qBP mediates inhibition of purinergic signaling—and ICV TLQP-21 reduces amyloid pathology in 5xFAD Alzheimer mice.

    Evidence C3aR1-null microglia RNA-seq, phagocytosis/migration assays, patch clamp in brain slices, C1qBP antagonists, ICV osmotic pump delivery in 5xFAD mice

    PMID:31924226 PMID:32060170

    Open questions at the time
    • Mechanism of amyloid clearance (direct phagocytosis vs. indirect neuroprotection) not fully resolved
    • Human genetic evidence linking VGF to Alzheimer risk is associative, not causal
  20. 2021 High

    An mTOR-dependent translational autoregulatory loop was discovered: TLQP-62 or fear memory training rapidly increases VGF protein via mTOR-dependent polysome loading without changing mRNA; the 3′UTR represses translation, and mice with truncated 3′UTR have enhanced VGF protein, improved memory, and reduced depression-like behavior.

    Evidence Polysome profiling, 3′UTR luciferase reporters, Vgf 3′UTR-truncation knock-in mice, rapamycin, behavioral testing

    PMID:34238925

    Open questions at the time
    • RNA-binding proteins or miRNAs mediating 3′UTR repression not identified
    • Whether this translational control operates in non-neuronal VGF-expressing cells unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the direct receptor for TLQP-62 has not been identified; structural details of TLQP-21 binding to C3aR1 and C1qBP are lacking; the molecular mechanism by which full-length VGF promotes dense-core vesicle biogenesis at the trans-Golgi network remains unknown; and whether VGF peptides vs. the intact precursor protein mediate granule formation has not been separated.
  • TLQP-62 receptor identity unknown
  • No structural model for TLQP-21–receptor complexes
  • Granule biogenesis mechanism at molecular level uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 6 GO:0098772 molecular function regulator activity 2
Localization
GO:0005576 extracellular region 5 GO:0031410 cytoplasmic vesicle 4 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-74160 Gene expression (Transcription) 5 R-HSA-112316 Neuronal System 4 R-HSA-1430728 Metabolism 4 R-HSA-162582 Signal Transduction 4 R-HSA-392499 Metabolism of proteins 4 R-HSA-168256 Immune System 3 R-HSA-9609507 Protein localization 3
Partners
ASCL1C1QBPC3AR1CREB1EP300PCSK1PCSK2TCF12

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 VGF gene transcription is rapidly and selectively induced by NGF (and basic FGF) in PC12 cells via a cAMP response element (CRE) in the promoter; induction also occurs with depolarization and PMA. The promoter contains TATAA, CCAAT elements, GC boxes, and a consensus CRE-binding protein site. Northern/RNase protection analysis, promoter cloning and sequencing, transcription reporter assays in PC12 cells Molecular and cellular biology High 2017159
1992 NGF induces VGF gene expression at the transcriptional level through a consensus CRE embedded in a 14-bp palindrome immediately upstream of the transcription start site; mutation of this CRE eliminates induction by both NGF and cAMP. This element selectively responds to NGF/cAMP but not EGF, FGF, or PMA. The inducible transcription factor CREB binds this CRE. Promoter mutagenesis, transient transfection reporter assays, EMSA (CREB binding), pharmacological treatments in PC12 cells The Journal of neuroscience High 1377233
1992 VGF gene induction by NGF requires ongoing protein synthesis (transcription-dependent), is partly repressed in non-neuronal cells by a nuclear repressor, and a 110-bp promoter region contains both positive and negative regulatory elements. A 47-bp oligonucleotide within this region specifically binds nuclear proteins that differ between VGF-expressing and non-expressing cells. Transcriptional run-on, promoter-reporter transfection, EMSA with cell-type-specific nuclear extracts, protein synthesis inhibition Proceedings of the National Academy of Sciences High 1570299
1995 VGF precursor undergoes tissue-specific proteolytic processing in a post-ER compartment to produce low-molecular-weight species (~20, 18, 10 kDa). These processed forms are enriched in secretory vesicles and preferentially secreted upon membrane depolarization, indicating regulated release from dense core vesicles. Immunoblotting with N- and C-terminal antisera, subcellular fractionation, depolarization-induced secretion assays in cerebellar granule cells and PC12 cells Journal of neurochemistry High 7595538
1996 VGF transcriptional induction by NGF is mediated through a Ras-dependent signaling pathway. Three promoter elements are required: a CRE (binding ATF-1, ATF-2, CREB), a novel CCAAT element, and a G(S)G element between the TATA box and transcription start site that binds the NGF/Ras-induced transcription factor NGFI-A. All three are necessary but no single element is sufficient. Chimeric vgf/beta-globin reporter gene transfection, dominant-interfering and activated Ras mutants, TrkA mutants, promoter deletional/mutational analysis, EMSA Molecular and cellular biology High 8756618
1997 VGF promoter regulation involves cooperative binding of an E-box (binding HTF4/HEB E-protein as part of a multiprotein complex) and a CRE; the E-box acts as a repressor in non-neuronal (NIH 3T3) cells but as a stimulator in NGF-responsive PC12 cells. A neuro-specific bHLH transcription factor (MASH1) participates in neurotrophin-dependent transcription via the CCAAT motif. EMSA, expression cDNA cloning, reporter gene transfection, mutational analysis of E-box and CRE Molecular and cellular biology High 9032251
1999 VGF knockout mice are lean, hypermetabolic, hyperactive, and infertile with markedly reduced leptin levels, fat stores, and altered hypothalamic POMC, NPY, and AGRP expression, establishing a non-redundant role for VGF in energy homeostasis. VGF mRNA is induced in hypothalamic arcuate nuclei upon fasting. Targeted gene deletion (knockout mice), metabolic phenotyping, in situ hybridization Neuron High 10433265
1999 VGF is expressed in insulin-secreting INS-1 beta cells, where it is processed in a post-ER compartment and its peptides are released via a regulated secretory pathway upon stimulation with glucose, cAMP, or PMA. VGF mRNA in INS-1 cells is transcriptionally upregulated by increased intracellular cAMP but not by glucose or NGF. RT-PCR, metabolic labeling, immunoprecipitation, secretion assays in INS-1 cells Endocrinology High 10433233
2002 PC1/3 and PC2 prohormone convertases process the VGF precursor: both generate VGF20 (a ~20 kDa C-terminal fragment), while VGF10 is preferentially produced by PC1/3. The KRKRKK(488) motif is the target cleavage site generating VGF20 (identified by site-directed mutagenesis); VGF10 results from cleavage at RPR(555). Two additional novel VGF peptides were identified in rat brain by MALDI-ToF MS and Edman degradation. Ectopic expression of PC1/3 or PC2 in GH3 cells, site-directed mutagenesis of VGF cleavage sites, MALDI-ToF MS, Edman degradation Journal of neurochemistry High 12065665
2002 VGF and POMC are co-expressed in lateral arcuate neurons in fed state; VGF expression is induced in medial arcuate NPY neurons after fasting. VGF mRNA induction in fasted mice is inhibited by exogenous leptin, and is elevated in leptin-deficient ob/ob and db/db mice. VGF deficiency completely blocks obesity in agouti (Ay/a) mice but only attenuates weight gain in ob/ob mice, placing VGF downstream of melanocortin 4 receptors in autonomic outflow pathways. Double-label in situ hybridization, genetic epistasis (VGF KO × Ay/a, ob/ob, db/db crosses), leptin injection, gold thioglucose and diet-induced obesity models The Journal of neuroscience High 12177191
2002 NGF-dependent and tissue-specific transcription of vgf is regulated by a CREB-p300 complex and a bHLH factor interaction. In non-neuronal cells, HEB (ubiquitous bHLH) and p300 form a repressor complex at the promoter. In neuronal cells, neurotrophin-dependent transcription is mediated by a distinct complex containing CREB, MASH1 (neuro-specific bHLH), and p300 bound to the CCAAT motif. Co-immunoprecipitation, EMSA, chromatin immunoprecipitation, reporter gene transfection, dominant-negative approaches FEBS letters High 11755530
2005 VGF sorting into the regulated secretory pathway (large dense core vesicles, LDCVs) requires a compact C-terminal alpha-helix and an embedded 564RRR566 prohormone convertase cleavage site. Mutation of 564RRR566 blocks regulated secretion; mutation of adjacent 567HFHH570 also blocks regulated release. Inhibition of PC cleavage by membrane-permeable chloromethyl ketone (decanoyl-RVKR-CMK) blocks regulated VGF secretion. Deletional and site-directed mutagenesis of VGF, confocal microscopy, subcellular fractionation, pharmacological PC inhibition in PC12 and INS-1 cells The Journal of biological chemistry High 16221685
2006 The VGF-derived peptide TLQP-21 (identified in rat brain by immunoprecipitation/LC-MS/MS) increases resting energy expenditure and rectal temperature upon chronic ICV injection in mice, preventing diet-induced obesity. TLQP-21 acts by stimulating autonomic activation of the adrenal medulla, upregulating brown adipose tissue beta2-AR and white adipose tissue PPAR-delta, beta3-AR, and UCP1 mRNAs, independently of thyroid hormones or locomotor activity. LC-MS/MS peptide identification, chronic ICV injection, indirect calorimetry, gene expression (RT-PCR), hormonal measurements Proceedings of the National Academy of Sciences High 16983076
2008 The VGF C-terminal peptide TLQP-62 induces transient potentiation in rat hippocampal slices through a mechanism blocked by the BDNF scavenger TrkB-Fc, Trk kinase inhibitor K252a, and tPA inhibitor tPASTOP, but not by NMDA receptor antagonist APV or anti-p75NTR. VGF knockout mice cannot undergo hippocampal LTD and show impaired spatial learning and contextual fear conditioning. Electrophysiology in hippocampal slices (LTP/LTD), pharmacological blockade with specific inhibitors, VGF KO behavioral testing (Morris water maze, fear conditioning) The Journal of neuroscience High 18815270
2009 VGF-derived peptides AQEE-30 and LQEQ-19 evoke dose-dependent thermal hyperalgesia upon intrathecal injection via activation of p38 MAP kinase. LQEQ-19 induces p38 phosphorylation in spinal microglia in vivo and in BV-2 microglial cells in vitro. VGF protein levels are rapidly upregulated in dorsal root ganglion neurons after nerve injury and hindpaw inflammation. Intrathecal peptide injection, thermal hyperalgesia assays, p38 immunostaining/phospho-western, proteomics of DRG neurons The Journal of neuroscience High 19846725
2009 NERP-1 and NERP-2, novel bioactive peptides derived from VGF, co-localize with vasopressin in storage granules of paraventricular and supraoptic hypothalamic nuclei. Administration of NERPs suppresses vasopressin release from hypothalamus and pituitary induced by hypertonic saline or angiotensin II. Immunohistochemistry/co-localization, in vivo and ex vivo vasopressin secretion assays Cellular and molecular life sciences Medium 19194657
2012 TLQP-21 promotes lipolysis in murine white adipose tissue (WAT) via a saturable receptor-binding mechanism that requires activation of noradrenaline/beta-adrenergic receptor pathways. VGF immunoreactivity is present in sympathetic nerve fibers innervating WAT but not in adipocytes. TLQP-21 binding capacity is higher in WAT than other tissues and is upregulated in obese mice. Receptor binding assays (saturation binding), lipolysis assays in primary adipocytes, immunohistochemistry, in vivo injection in obesity models The Biochemical journal High 21880012
2012 Nkx6.1 strongly upregulates VGF in rat islets, and VGF is necessary and sufficient for Nkx6.1-mediated enhancement of glucose-stimulated insulin secretion (GSIS). The VGF-derived peptide TLQP-21 potentiates GSIS in rat and human islets and improves glucose tolerance in vivo. Chronic TLQP-21 injection in prediabetic ZDF rats preserves islet mass. TLQP-21 prevents islet apoptosis by a GLP-1/GIP/VIP receptor-independent pathway similar to that of GLP-1. Overexpression/knockdown of VGF in rat islets, GSIS assays, receptor antagonist studies, in vivo ZDF rat treatment, apoptosis assays Cell metabolism High 22768837
2013 C3a receptor-1 (C3AR1) is a G protein-coupled receptor target for the VGF-derived peptide TLQP-21 in rodent cells. Identified by unbiased genome-wide transcriptome sequencing of responsive CHO-K1 cells, confirmed by siRNA knockdown and receptor antagonists. TLQP-21 signaling through C3AR1 is pertussis toxin-sensitive (consistent with Gi/o coupling) and directs migration of mouse RAW264.7 macrophages. Unbiased RNA-seq-based receptor deorphanization, siRNA knockdown, receptor antagonists, pertussis toxin, cell migration assays The Journal of biological chemistry High 23940034
2013 gC1qR (globular heads of the C1q receptor) is a receptor for the VGF-derived peptide TLQP-21, identified by chemical cross-linking combined with mass spectrometry. TLQP-21 causes increased intracellular Ca2+ in rat macrophages and microglia via gC1qR. TLQP-21-stimulated macrophages cause mechanical hypersensitivity when inoculated into rat hind paw; gC1qR-neutralizing antibody attenuates neuropathic pain in partial sciatic nerve ligation. Chemical cross-linking/mass spectrometry, siRNA knockdown, neutralizing antibodies, intracellular Ca2+ imaging, in vivo pain model The Journal of biological chemistry High 24106277
2014 TLQP-21 induces thermal hyperalgesia via p38 MAP kinase and is inhibited by cyclooxygenase and lipoxygenase inhibitors. Immunoneutralization of endogenous TLQP-21 by intrathecal anti-TLQP-21 antibody inhibits tactile hypersensitivity and thermal hyperalgesia in CFA-induced inflammation and spared nerve injury neuropathic pain models, demonstrating that endogenous TLQP-21 contributes to spinal pain sensitization. Intrathecal peptide/antibody administration, von Frey and thermal withdrawal assays, pharmacological inhibitors (p38, COX, LOX) in CFA and SNI mouse models Pain High 24657450
2014 The granin VGF promotes biogenesis of large dense core vesicles (LDCVs) in the adrenal medulla. VGF knockout mice have decreased LDCV size in noradrenergic chromaffin cells, increased adrenal norepinephrine and epinephrine content, elevated plasma epinephrine, decreased adrenal chromogranin B, and hypertension. Expression of exogenous VGF in NIH 3T3 fibroblasts generates LDCV-like structures with depolarization-induced secretion. Knock-in of human VGF1-615 rescues the hypertensive phenotype; knock-in of truncated VGF1-524 (lacking TLQP-21) only partially rescues it. Acute and chronic TLQP-21 administration decreases blood pressure. Germline VGF KO and humanized knock-in mice, electron microscopy of adrenal chromaffin cells, catecholamine measurements, blood pressure telemetry, VGF overexpression in NIH 3T3 fibroblasts, peptide administration FASEB journal High 24497580
2015 VGF expression and secretion of C-terminal peptide TLQP-62 in hippocampus are transiently induced after fear memory training. Sequestering TLQP-62 after training impairs memory formation. TLQP-62 induces acute TrkB receptor phosphorylation and subsequent CREB phosphorylation in hippocampal slices. TLQP-62's memory-enhancing effect is rescued by BDNF-TrkB signaling activation and is VGF-dependent (germline or antibody-sequestration experiments). VGF-deficient mice show impaired Rac1 induction and reduced cofilin/synapsin phosphorylation after learning. In vivo fear conditioning, intra-hippocampal antibody infusion, hippocampal slice TrkB phosphorylation assays, VGF KO mice, BDNF rescue experiments, signaling pathway analysis (Rac1, cofilin, synapsin) The Journal of neuroscience High 26180209
2017 VGF regulates insulin secretory granule biogenesis in pancreatic beta cells. Conditional VGF knockout in islets and beta-cell-specific knockout mice show profound decreases in stimulus-coupled insulin secretion. VGF is required for efficient exit of granule cargo from the trans-Golgi network, for proinsulin processing, and for replenishment of insulin granule stores after nutrient stimulation. Conditional KO (floxed VGF mice + Cre), islet secretion assays, electron microscopy of secretory granules, proinsulin processing analysis, trans-Golgi network trafficking assays Cell reports High 28877479
2017 VGF regulates depression-like behavior in dorsal hippocampus (dHc) and nucleus accumbens (NAc) in opposite directions: dHc VGF ablation produces pro-depressant behavior and dHc VGF overexpression produces antidepressant behavior; NAc VGF ablation is antidepressant and overexpression is pro-depressant. The antidepressant efficacy of ketamine requires VGF expression and is associated with rapid VGF translation. TLQP-62 antidepressant effects in dHc require AMPA receptor and mTOR signaling (blocked by NBQX and rapamycin). Conditional pan-neuronal (but not forebrain) VGF ablation increases stress susceptibility, indicating neuronal (partially inhibitory interneuron) VGF regulates depression. AAV-Cre conditional KO and overexpression in floxed VGF mice (region-specific), germline VGF heterozygous mice, social defeat stress, forced swim test, AMPA/mTOR pharmacological inhibitors, Synapsin-Cre and αCaMKII-Cre crosses Molecular psychiatry High 29158577
2020 TLQP-21 increases motility and phagocytic capacity in murine microglia via C3aR1 signaling. C3aR1-null primary microglia have impaired basal phagocytic function; TLQP-21 and C3a super agonist induce overlapping transcriptomic changes (migration/proliferation genes) in wild-type but not C3aR1-null microglia. ICV TLQP-21 in 5xFAD mice reduces amyloid plaques, associated dystrophic neurites, and restores Alzheimer-associated microglial gene expression. Human TLQP-21 activates human microglia similarly to mouse TLQP-21. Phagocytosis/migration assays, RNA-seq of primary microglia (WT vs. C3aR1-null), osmotic pump ICV delivery in 5xFAD mice, immunohistochemistry for amyloid plaques, human HMC3 microglial cell line assays Molecular neurodegeneration High 31924226
2020 TLQP-21 impairs metabotropic purinergic (P2Y) signaling in microglia in acute brain slices, attenuating ATP-induced K+ conductance, UDP-stimulated phagocytosis, and ATP-dependent process outgrowth toward injury. These impairments are reversed by blocking C1qBP but not C3aR1. In cultured microglia (which express both receptors), TLQP-21 additionally evokes Ca2+ transients, membrane currents, and chemotaxis via C3aR1, demonstrating dual receptor-dependent effects. Whole-cell patch clamp in brain slices, phagocytosis assays, laser lesion-induced process outgrowth imaging, Ca2+ imaging, C1qBP and C3aR1 antagonists, primary microglia from C3aR1-null mice The Journal of neuroscience High 32060170
2020 SOX9 drives injury-induced transcriptional upregulation of VGF in renal tubular epithelial cells (RTECs). RTEC-specific Vgf gene ablation exacerbates ischemia-, cisplatin-, and rhabdomyolysis-induced acute kidney injury in vivo and cisplatin-induced RTEC death in vitro. Aggravation of cisplatin injury by Vgf ablation is partly reversed by exogenous TLQP-21 peptide. Renal transcriptome profiling in three AKI mouse models, RTEC-specific conditional KO, in vitro cell death assays, SOX9 ChIP/reporter assays, TLQP-21 rescue experiments The Journal of biological chemistry High 32887795
2021 TLQP-62 or contextual fear memory training acutely increases translation of VGF and other granin proteins (CgB, Scg2) via mTOR-dependent signaling without measurable increases in mRNA, constituting a transcription-independent autofeedback mechanism. The 3'UTR of Vgf mRNA represses VGF translation (validated by luciferase reporter). Mice with truncated endogenous Vgf 3'UTR show substantially increased VGF protein, enhanced memory performance, and reduced anxiety/depression-like behaviors. Polysome/translation assays, luciferase 3'UTR reporter assays, Vgf 3'UTR-truncation knock-in mice, mTOR inhibition (rapamycin), fear conditioning behavioral assays Translational psychiatry High 34238925
2008 The VGF-derived peptide TLQP-21 promotes survival of rat cerebellar granule cells (CGCs) against serum/potassium deprivation-induced apoptosis in a dose- and time-dependent manner. Neuroprotection is associated with activation of ERK1/2, Akt (serine/threonine kinase), and JNK phosphorylation, decreased PKC phosphorylation, and increased intracellular Ca2+ in ~60% of neurons. Cell viability assays, DNA fragmentation (apoptosis), western blot for kinase phosphorylation, fura-2AM Ca2+ imaging in primary CGC cultures Journal of neurochemistry Medium 18173805
2014 TLQP-62 induces proliferation of early-phase (Type 2a nestin+) neural progenitor cells in the adult hippocampus via NMDA receptor- and mGluR5-dependent glutamate signaling, activating CaMKII and PKD, respectively. TLQP-62 also gradually activates TrkB (BDNF receptor), and TrkB signaling is required for TLQP-62-induced NPC proliferation. Nestin-GFP reporter mice, BrdU/thymidine incorporation, NPC proliferation assays in vitro (cell line and primary progenitors), pharmacological NMDA/mGluR5/CaMKII/PKD inhibitors, Cyclin D qPCR, TrkB inhibitors Stem cell research High 24747217
2016 Voluntary running induces VGF expression in the brain, which promotes oligodendrogenesis in the cerebellum of Snf2h conditional knockout ataxic mice, prolonging survival. VGF neuropeptides promote oligodendrogenesis in vitro, and adenoviral VGF overexpression in vivo rescues survival without requiring exercise. Conditional Snf2h KO mice, voluntary wheel running, VGF adenoviral overexpression, oligodendrocyte lineage cell counts, in vitro oligodendrogenesis assays Cell reports High 27732860
2009 TLQP-21 induces contraction of rat forestomach smooth muscle by releasing prostaglandins PGE2 and PGF2a from the mucosal layer, blocked by indomethacin and selective COX-1/COX-2 inhibitors. ICV TLQP-21 decreases gastric emptying by ~40% via central PG release. VGF immunoreactivity is present in gastric neuronal cells. Isolated smooth muscle preparation, in vitro contraction assays, pharmacological inhibitors (indomethacin, COX-1/2), in vivo ICV injection, gastric emptying measurement, immunostaining British journal of pharmacology Medium 19466987
2018 VGF and TLQP-62 in ventromedial prefrontal cortex (vmPFC) regulate stress susceptibility and antidepressant response to ketamine. TLQP-62 antidepressant-like effects in vmPFC require BDNF expression and calcium mobilization (blocked by xestospongin C, an IP3 receptor inhibitor, and SKF96365, a TRPC/store-operated channel inhibitor), revealing a calcium-dependent signaling mechanism downstream of TLQP-62/BDNF. AAV-Cre conditional VGF KO and overexpression in floxed VGF mice (vmPFC), intra-vmPFC TLQP-62 infusion, Bdnf conditional KO, pharmacological Ca2+ pathway inhibitors, chronic restraint stress, subchronic variable stress Neuropsychopharmacology High 30504797
2019 lncRNA H19 binds VGF protein (demonstrated by RNA pulldown and mass spectrometry) and promotes pancreatic neuroendocrine neoplasm (pNEN) cell proliferation, migration and invasion. VGF activated PI3K/AKT/CREB signaling; H19 activates this signaling pathway via VGF, and VGF knockdown reduces these oncogenic phenotypes. RNA pulldown/mass spectrometry, RIP, siRNA knockdown, in vitro proliferation/migration/invasion assays, RNA-seq, in vivo xenograft Endocrine-related cancer Medium 31117050
1989 VGF immunoreactivity in the hypothalamus co-localizes with vasopressin or vasoactive intestinal polypeptide in SCN neurons, and with oxytocin or vasopressin in paraventricular and supraoptic nuclei. Ultrastructural studies show VGF immunoreactivity in presynaptic boutons in SCN and in axons of the neurohypophysis, consistent with a secretory neuropeptide role. Immunocytochemistry with two non-overlapping antisera, colchicine axonal transport blockade, co-localization by immunofluorescence, electron microscopy The Journal of neuroscience High 2556505
1996 VGF is localized to a subpopulation of large dense core vesicles in PC12 cells (by electron microscopy). In developing hippocampal neurons, VGF-containing vesicles are present from earliest developmental stages and are particularly abundant in GABAergic neurons; VGF becomes restricted to axons after dendrites mature (associated with synaptogenesis, not axonal polarization). VGF-containing and synaptophysin-containing vesicles are distinct and differentially distributed. Electron microscopy immunolabeling in PC12 cells, immunofluorescence co-localization in hippocampal neurons, developmental staging Brain research. Developmental brain research Medium 8922684

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 Antidepressant actions of the exercise-regulated gene VGF. Nature medicine 210 18059283
1999 Targeted deletion of the Vgf gene indicates that the encoded secretory peptide precursor plays a novel role in the regulation of energy balance. Neuron 191 10433265
2000 VGF: a novel role for this neuronal and neuroendocrine polypeptide in the regulation of energy balance. Frontiers in neuroendocrinology 143 10882540
2020 Multiscale causal networks identify VGF as a key regulator of Alzheimer's disease. Nature communications 134 32770063
1991 Structure of the gene encoding VGF, a nervous system-specific mRNA that is rapidly and selectively induced by nerve growth factor in PC12 cells. Molecular and cellular biology 133 2017159
2007 The neuropeptide VGF produces antidepressant-like behavioral effects and enhances proliferation in the hippocampus. The Journal of neuroscience : the official journal of the Society for Neuroscience 132 17989282
2008 The neurotrophin-inducible gene Vgf regulates hippocampal function and behavior through a brain-derived neurotrophic factor-dependent mechanism. The Journal of neuroscience : the official journal of the Society for Neuroscience 128 18815270
2004 Processing, distribution, and function of VGF, a neuronal and endocrine peptide precursor. Cellular and molecular neurobiology 128 15233376
2006 TLQP-21, a VGF-derived peptide, increases energy expenditure and prevents the early phase of diet-induced obesity. Proceedings of the National Academy of Sciences of the United States of America 125 16983076
1988 Cell proliferative response to vaccinia virus is mediated by VGF. Virology 116 3363864
2014 Antidepressant effects of crocin and its effects on transcript and protein levels of CREB, BDNF, and VGF in rat hippocampus. Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences 114 24401376
2017 VGF function in depression and antidepressant efficacy. Molecular psychiatry 97 29158577
2002 Isolation and characterization of VGF peptides in rat brain. Role of PC1/3 and PC2 in the maturation of VGF precursor. Journal of neurochemistry 94 12065665
2015 VGF and Its C-Terminal Peptide TLQP-62 Regulate Memory Formation in Hippocampus via a BDNF-TrkB-Dependent Mechanism. The Journal of neuroscience : the official journal of the Society for Neuroscience 92 26180209
1989 Hypothalamic expression of a novel gene product, VGF: immunocytochemical analysis. The Journal of neuroscience : the official journal of the Society for Neuroscience 91 2556505
2002 VGF is required for obesity induced by diet, gold thioglucose treatment, and agouti and is differentially regulated in pro-opiomelanocortin- and neuropeptide Y-containing arcuate neurons in response to fasting. The Journal of neuroscience : the official journal of the Society for Neuroscience 86 12177191
2013 Identification of the C3a receptor (C3AR1) as the target of the VGF-derived peptide TLQP-21 in rodent cells. The Journal of biological chemistry 81 23940034
2007 VGF-derived peptide, TLQP-21, regulates food intake and body weight in Siberian hamsters. Endocrinology 81 17463057
2012 A VGF-derived peptide attenuates development of type 2 diabetes via enhancement of islet β-cell survival and function. Cell metabolism 78 22768837
2021 VGF as a biomarker and therapeutic target in neurodegenerative and psychiatric diseases. Brain communications 76 34778762
2020 VGF-derived peptide TLQP-21 modulates microglial function through C3aR1 signaling pathways and reduces neuropathology in 5xFAD mice. Molecular neurodegeneration 74 31924226
2004 Photoperiodic regulation of histamine H3 receptor and VGF messenger ribonucleic acid in the arcuate nucleus of the Siberian hamster. Endocrinology 74 15618354
1992 NGF induces the expression of the VGF gene through a cAMP response element. The Journal of neuroscience : the official journal of the Society for Neuroscience 73 1377233
2008 Neuropeptides in depression: role of VGF. Behavioural brain research 69 18983874
1995 Tissue-specific processing of the neuroendocrine protein VGF. Journal of neurochemistry 69 7595538
2015 Neuroendocrine Role for VGF. Frontiers in endocrinology 68 25699015
2010 Distribution of VGF peptides in the human cortex and their selective changes in Parkinson's and Alzheimer's diseases. Journal of anatomy 65 21039478
1994 VGF expression in the brain. The Journal of comparative neurology 65 7822494
2010 The expression of VGF is reduced in leukocytes of depressed patients and it is restored by effective antidepressant treatment. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 64 20164831
2014 Antidepressant Effect of Crocus sativus Aqueous Extract and its Effect on CREB, BDNF, and VGF Transcript and Protein Levels in Rat Hippocampus. Drug research 63 24696423
2011 VGF: an inducible gene product, precursor of a diverse array of neuro-endocrine peptides and tissue-specific disease biomarkers. Journal of chemical neuroanatomy 63 21621608
2014 Rapid-acting antidepressant-like effects of acetyl-l-carnitine mediated by PI3K/AKT/BDNF/VGF signaling pathway in mice. Neuroscience 62 25463525
2014 PI3K/AKT/mTOR signaling-mediated neuropeptide VGF in the hippocampus of mice is involved in the rapid onset antidepressant-like effects of GLYX-13. The international journal of neuropsychopharmacology 61 25542689
2013 Identification of a receptor for neuropeptide VGF and its role in neuropathic pain. The Journal of biological chemistry 55 24106277
2012 Characterization of a novel peripheral pro-lipolytic mechanism in mice: role of VGF-derived peptide TLQP-21. The Biochemical journal 54 21880012
1998 The messenger RNA encoding VGF, a neuronal peptide precursor, is rapidly regulated in the rat central nervous system by neuronal activity, seizure and lesion. Neuroscience 54 9483499
2014 The VGF-derived peptide TLQP62 produces antidepressant-like effects in mice via the BDNF/TrkB/CREB signaling pathway. Pharmacology, biochemistry, and behavior 53 24631486
2014 VGF (TLQP-62)-induced neurogenesis targets early phase neural progenitor cells in the adult hippocampus and requires glutamate and BDNF signaling. Stem cell research 53 24747217
2017 Expression of Neuroendocrine Factor VGF in Lung Cancer Cells Confers Resistance to EGFR Kinase Inhibitors and Triggers Epithelial-to-Mesenchymal Transition. Cancer research 51 28381546
2008 TLQP-21, a neuroendocrine VGF-derived peptide, prevents cerebellar granule cells death induced by serum and potassium deprivation. Journal of neurochemistry 50 18173805
1992 Regulatory elements in the promoter region of vgf, a nerve growth factor-inducible gene. Proceedings of the National Academy of Sciences of the United States of America 50 1570299
2017 The Prohormone VGF Regulates β Cell Function via Insulin Secretory Granule Biogenesis. Cell reports 49 28877479
2010 An inducer of VGF protects cells against ER stress-induced cell death and prolongs survival in the mutant SOD1 animal models of familial ALS. PloS one 48 21151573
1999 Expression, processing, and secretion of the neuroendocrine VGF peptides by INS-1 cells. Endocrinology 47 10433233
2018 Role of a VGF/BDNF/TrkB Autoregulatory Feedback Loop in Rapid-Acting Antidepressant Efficacy. Journal of molecular neuroscience : MN 46 30022437
2009 Proteomic analysis uncovers novel actions of the neurosecretory protein VGF in nociceptive processing. The Journal of neuroscience : the official journal of the Society for Neuroscience 46 19846725
2005 VGF ablation blocks the development of hyperinsulinemia and hyperglycemia in several mouse models of obesity. Endocrinology 44 16141392
2010 The neuropeptide VGF is reduced in human bipolar postmortem brain and contributes to some of the behavioral and molecular effects of lithium. The Journal of neuroscience : the official journal of the Society for Neuroscience 42 20631166
2009 In vitro and in vivo pharmacological role of TLQP-21, a VGF-derived peptide, in the regulation of rat gastric motor functions. British journal of pharmacology 42 19466987
1998 Developmental expression of VGF mRNA in the prenatal and postnatal rat. The Journal of comparative neurology 42 9550143
2014 The granin VGF promotes genesis of secretory vesicles, and regulates circulating catecholamine levels and blood pressure. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 41 24497580
2007 The role of the vgf gene and VGF-derived peptides in nutrition and metabolism. Genes & nutrition 41 18850173
1995 The "VGF" protein in rat adenohypophysis: sex differences and changes during the estrous cycle and after gonadectomy. Endocrinology 41 7720674
1993 In situ hybridization: mRNA levels of secretogranin II, VGF and peptidylglycine alpha-amidating monooxygenase in brain of salt-loaded rats. Histochemistry 40 8500992
2022 Biocompatible exosome-modified fibrin gel accelerates the recovery of spinal cord injury by VGF-mediated oligodendrogenesis. Journal of nanobiotechnology 39 35918769
2014 The VGF-derived peptide TLQP-21 contributes to inflammatory and nerve injury-induced hypersensitivity. Pain 39 24657450
2008 Origins, actions and dynamic expression patterns of the neuropeptide VGF in rat peripheral and central sensory neurones following peripheral nerve injury. Molecular pain 39 19077191
2016 Voluntary Running Triggers VGF-Mediated Oligodendrogenesis to Prolong the Lifespan of Snf2h-Null Ataxic Mice. Cell reports 38 27732860
1995 A developmentally regulated nerve growth factor-induced gene, VGF, is expressed in geniculocortical afferents during synaptogenesis. Neuroscience 38 7617174
2018 VGF and its C-terminal peptide TLQP-62 in ventromedial prefrontal cortex regulate depression-related behaviors and the response to ketamine. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 37 30504797
2017 Neuropeptide VGF C-Terminal Peptide TLQP-62 Alleviates Lipopolysaccharide-Induced Memory Deficits and Anxiety-like and Depression-like Behaviors in Mice: The Role of BDNF/TrkB Signaling. ACS chemical neuroscience 37 28594546
2013 Association of promoter methylation of VGF and PGP9.5 with ovarian cancer progression. PloS one 35 24086249
2009 Analysis of knockout mice suggests a role for VGF in the control of fat storage and energy expenditure. BMC physiology 34 19863797
1997 Regulation of the vgf gene in the golden hamster suprachiasmatic nucleus by light and by the circadian clock. The Journal of comparative neurology 33 9120062
1994 Peptide V: a VGF-derived neuropeptide purified from bovine posterior pituitary. Endocrinology 33 7988466
1991 Nucleotide sequence and regulatory studies of VGF, a nervous system-specific mRNA that is rapidly and relatively selectively induced by nerve growth factor. Journal of neurochemistry 33 1861162
2007 VGF metabolic-related gene: distribution of its derived peptides in mammalian pancreatic islets. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 31 17312015
2022 Effects of neuronavigation-guided rTMS on serum BDNF, TrkB and VGF levels in depressive patients with suicidal ideation. Journal of affective disorders 30 36462609
2020 Pathologically Decreased CSF Levels of Synaptic Marker NPTX2 in DLB Are Correlated with Levels of Alpha-Synuclein and VGF. Cells 30 33383752
2001 Regional differences in neurotrophin availability regulate selective expression of VGF in the developing limbic cortex. The Journal of neuroscience : the official journal of the Society for Neuroscience 30 11717365
2021 In vitro and in vivo optimization of liposomal nanoparticles based brain targeted vgf gene therapy. International journal of pharmaceutics 29 34543617
2019 VGF in Cerebrospinal Fluid Combined With Conventional Biomarkers Enhances Prediction of Conversion From MCI to AD. Alzheimer disease and associated disorders 29 31305322
1997 Interplay of the E box, the cyclic AMP response element, and HTF4/HEB in transcriptional regulation of the neurospecific, neurotrophin-inducible vgf gene. Molecular and cellular biology 29 9032251
1996 Activation of codependent transcription factors is required for transcriptional induction of the vgf gene by nerve growth factor and Ras. Molecular and cellular biology 29 8756618
2019 VGF Peptides in Cerebrospinal Fluid of Patients with Dementia with Lewy Bodies. International journal of molecular sciences 28 31547145
1996 Expression and polarization of VGF in developing hippocampal neurons. Brain research. Developmental brain research 28 8922684
2020 SOX9 promotes stress-responsive transcription of VGF nerve growth factor inducible gene in renal tubular epithelial cells. The Journal of biological chemistry 27 32887795
2017 Study of the Role of CREB, BDNF, and VGF Neuropeptide in Long Term Antidepressant Activity of Crocin in the Rat Cerebellum. Iranian journal of pharmaceutical research : IJPR 27 29552054
1993 Messenger RNA levels of chromogranin B, secretogranin II, and VGF in rat brain after AF64A-induced septohippocampal cholinergic lesions. Journal of neurochemistry 27 8228984
2016 Role of Hypothalamic VGF in Energy Balance and Metabolic Adaption to Environmental Enrichment in Mice. Endocrinology 26 26730934
2008 Role of VGF-derived peptides in the control of food intake, body weight and reproduction. Neuroendocrinology 26 18408361
2005 A prohormone convertase cleavage site within a predicted alpha-helix mediates sorting of the neuronal and endocrine polypeptide VGF into the regulated secretory pathway. The Journal of biological chemistry 26 16221685
2022 Synthesis and Characterization of Fatty Acid Grafted Chitosan Polymeric Micelles for Improved Gene Delivery of VGF to the Brain through Intranasal Route. Biomedicines 25 35203704
2020 The VGF-derived Peptide TLQP21 Impairs Purinergic Control of Chemotaxis and Phagocytosis in Mouse Microglia. The Journal of neuroscience : the official journal of the Society for Neuroscience 25 32060170
2010 Selective expression of TLQP-21 and other VGF peptides in gastric neuroendocrine cells and modulation by feeding. The Journal of endocrinology 25 20876237
2021 An increase in VGF expression through a rapid, transcription-independent, autofeedback mechanism improves cognitive function. Translational psychiatry 24 34238925
2011 Characterization of the reproductive effects of the anorexigenic VGF-derived peptide TLQP-21: in vivo and in vitro studies in male rats. American journal of physiology. Endocrinology and metabolism 24 21304062
2009 Neuroendocrine regulatory peptide-1 and -2: novel bioactive peptides processed from VGF. Cellular and molecular life sciences : CMLS 24 19194657
1997 Molecular cloning and characterization of the human VGF promoter region. Journal of neurochemistry 24 9084409
2017 Neuropeptide VGF Promotes Maturation of Hippocampal Dendrites That Is Reduced by Single Nucleotide Polymorphisms. International journal of molecular sciences 23 28287464
2017 Profiles of VGF Peptides in the Rat Brain and Their Modulations after Phencyclidine Treatment. Frontiers in cellular neuroscience 23 28626390
2011 Reduced density of hypothalamic VGF-immunoreactive neurons in schizophrenia: a potential link to impaired growth factor signaling and energy homeostasis. European archives of psychiatry and clinical neuroscience 23 22167530
2008 Differential distribution of VGF-derived peptides in the adrenal medulla and evidence for their selective modulation. The Journal of endocrinology 23 18434366
2002 NGF-dependent and tissue-specific transcription of vgf is regulated by a CREB-p300 and bHLH factor interaction. FEBS letters 23 11755530
2022 VGF: A prospective biomarker and therapeutic target for neuroendocrine and nervous system disorders. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 22 35594706
2016 VGF Protein and Its C-Terminal Derived Peptides in Amyotrophic Lateral Sclerosis: Human and Animal Model Studies. PloS one 22 27737014
2013 Characterization of the reproductive effects of the Vgf-derived peptide TLQP-21 in female rats: in vivo and in vitro studies. Neuroendocrinology 22 23485923
1996 vgf A neurotrophin-inducible gene expressed in neuroendocrine tissues. Trends in endocrinology and metabolism: TEM 22 18406753
2019 lncRNA H19 binds VGF and promotes pNEN progression via PI3K/AKT/CREB signaling. Endocrine-related cancer 21 31117050
2015 The VGF-derived peptide TLQP-62 modulates insulin secretion and glucose homeostasis. Journal of molecular endocrinology 21 25917832