Affinage

PDGFB

Platelet-derived growth factor subunit B · UniProt P01127

Length
241 aa
Mass
27.3 kDa
Annotated
2026-06-10
100 papers in source corpus 32 papers cited in narrative 32 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PDGFB (c-sis) encodes the B chain of platelet-derived growth factor, a secreted disulfide-linked dimeric mitogen that signals through cell-surface PDGF receptor tyrosine kinases to drive proliferative and chemotactic responses (PMID:6329745, PMID:6091918). The protein is matured through the ER-Golgi, where signal-sequence cleavage and N-linked glycosylation occur; it contains no transmembrane region, and proper signal-sequence-dependent trafficking is required for biological activity (PMID:3537701). In its viral oncogene form (v-sis), the product transforms cells by binding and autophosphorylating the PDGF receptor and inducing DNA synthesis, with transformation strictly contingent on receptor presence in the target cell and reversible by selective PDGF-receptor kinase inhibitors (PMID:6091918, PMID:2996133, PMID:7954456); this activating ligand-receptor interaction normally occurs at the plasma membrane, since blocking secretion or surface binding abolishes receptor autophosphorylation and c-fos induction, yet ER-retained, non-secreted mutants can also transform, demonstrating an additional intracellular autoactivation route (PMID:2455725, PMID:2551043). Downstream, PDGF-B engages a Ras/Raf-dependent, PKC-independent cascade to induce immediate-early genes and activates a dedicated sis-inducible factor (SIF) acting on the c-fos promoter independently of the serum-responsive element (PMID:2176154, PMID:7890805). Physiologically, PDGFB recruits and maintains mural-cell coverage of the vasculature: endothelial-, platelet-, microglia-, macrophage-, and lymphatic-endothelial-derived PDGFB directs pericyte and smooth-muscle-cell investment to stabilize blood vessels, with extracellular-matrix retention via its proteoglycan-binding motif essential for this recruitment (PMID:26599395, PMID:28851707, PMID:32586981, PMID:33591958). Microglia are the principal source sustaining adult blood-brain-barrier integrity, and loss-of-function PDGFB mutations that prevent synthesis or PDGFRβ binding cause primary familial brain calcification (PMID:26599395, PMID:37992789). PDGFB transcription is controlled by phorbol ester/PKC, TGF-β, mechanical strain, and defined factors acting on promoter elements including the SIS proximal element (PMID:2655888, PMID:8356057, PMID:10558917). In dermatofibrosarcoma protuberans, a COL1A1-PDGFB fusion places PDGFB under constitutive COL1A1-driven expression, generating an autocrine PDGFRβ loop that confers tumorigenicity and is sensitive to imatinib (PMID:9739023, PMID:11420709, PMID:11291071).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1984 High

    Establishing that the c-sis proto-oncogene encodes the PDGF B chain unified a transforming retroviral gene with a known mitogen, defining the molecular identity of PDGFB.

    Evidence Direct amino acid sequencing of purified PDGF B chain matched to c-sis genomic sequence

    PMID:6329745

    Open questions at the time
    • Did not address how the secreted protein engages receptors or drives transformation
    • No information on physiological tissue source
  2. 1985 High

    Demonstrating that the v-sis product binds the PDGF receptor, stimulates receptor tyrosine phosphorylation, and requires receptor presence for transformation defined an autocrine surface-receptor mechanism for sis-driven growth.

    Evidence Receptor binding, tyrosine phosphorylation, and DNA-synthesis assays with antibody inhibition and receptor-positive vs -negative cells

    PMID:2996133 PMID:6091918

    Open questions at the time
    • Did not resolve where activation occurs in the cell
    • Did not identify downstream effectors
  3. 1986 High

    Mapping the secretory processing route established that PDGFB matures through the ER-Golgi with signal cleavage and glycosylation and that correct trafficking is required for activity.

    Evidence Site-directed mutagenesis, microsome trypsin-protection, fractionation, immunofluorescence and transformation assays; membrane-anchored fusion analysis

    PMID:3536965 PMID:3537701

    Open questions at the time
    • Did not define the proteoglycan-binding/ECM-retention function later shown to be essential
    • Membrane-anchored form work is single-lab Medium confidence
  4. 1988 High

    Pharmacological blockade of secretion and surface binding localized the active signaling event to the plasma membrane, testing whether autocrine activation is intracellular or extracellular.

    Evidence Inducible v-sis expression with monensin/suramin and receptor autophosphorylation/c-fos readouts

    PMID:2455725

    Open questions at the time
    • Apparently contradicted by later ER-retention transformation data
    • Did not quantify relative contribution of surface vs internal routes
  5. 1989 High

    ER-retained, non-secreted v-sis mutants that still transform demonstrated an intracellular pre-surface receptor-activation route, qualifying the strict surface-only model.

    Evidence ER-retention signal mutagenesis, transformation assay, anti-PDGF antisera failing to reverse transformation

    PMID:2551043

    Open questions at the time
    • Did not define the subcellular site of intracellular activation
    • Relevance of internal activation to non-viral PDGFB unclear
  6. 1990 High

    Identification of a sis-inducible factor and the SIF promoter element defined a PDGF-B-specific transcriptional output distinct from the serum-response pathway.

    Evidence Recombinant PDGF-B induction, gel-shift, and c-fos promoter-reporter deletion analysis

    PMID:2176154

    Open questions at the time
    • Did not molecularly identify the SIF protein
    • Receptor-to-SIF signaling steps not defined
  7. 1994 High

    Genetic and pharmacological dissection placed PDGF-B signaling in a Ras/Raf-dependent, PKC-independent cascade and confirmed transformation runs specifically through PDGF-receptor kinase.

    Evidence Dominant-negative Ras/Raf in Egr-1 induction assays; selective tyrphostin reversion of sis-transformed cells with kinase-specificity profiling

    PMID:7890805 PMID:7954456

    Open questions at the time
    • Did not map full downstream effector network
    • Egr-1 epistasis is single-lab Medium confidence
  8. 1993 High

    Promoter dissection showed phorbol ester/PKC-, TGF-β-, and strain-responsive elements—including the SIS proximal element—control PDGFB transcription, defining its inducible regulation.

    Evidence Nuclear run-on, linker-scanning/deletion promoter mutagenesis, reporter and gel-shift assays, cycloheximide blockade; 5'UTR translational control

    PMID:2655888 PMID:2740212 PMID:3466024 PMID:8356057

    Open questions at the time
    • Identity of the SPE-binding factor not established
    • Mostly single-cell-type, single-lab analyses
  9. 1998 Medium

    Characterizing recurrent COL1A1-PDGFB fusions in DFSP showed how PDGFB is placed under constitutive COL1A1-promoter control with loss of its negative regulatory elements, linking PDGFB deregulation to a defined tumor.

    Evidence RT-PCR, sequencing, Southern blotting and breakpoint mapping across 16 DFSP/GCF tumors

    PMID:9739023

    Open questions at the time
    • Processing/functional consequence of exon-2 retention not directly tested here
    • Did not demonstrate autocrine loop functionally
  10. 2001 High

    Reconstitution proved the COL1A1-PDGFB chimera is processed to active PDGFB dimers driving an autocrine PDGFRβ loop conferring tumorigenicity, and that imatinib reverses this transformed phenotype.

    Evidence Stable/transient transfection, antibody immunodetection, receptor-activation assays, nude-mouse tumorigenicity, cleavage-site mutagenesis; STI571 treatment with washout reversal in vitro and in vivo

    PMID:11291071 PMID:11420709

    Open questions at the time
    • Imatinib effect is cytostatic and from a single lab
    • Contribution of uncleaved vs processed forms not fully quantified
  11. 2017 High

    Cell-type-specific deletion established that PDGFB recruits mural cells (pericytes, smooth muscle) and that its ECM-retention motif is required, defining the physiological vascular-stabilization function across vascular beds.

    Evidence LEC-specific Pdgfb conditional knockout, overexpression, ECM-retention mutant analysis, and vessel morphology/contraction phenotyping

    PMID:28851707

    Open questions at the time
    • Did not address adult maintenance vs developmental roles
    • Mechanism of ECM-dependent local gradient formation not detailed
  12. 2019 High

    Loss-of-function mutation analysis and Pdgfbret/ret mice tied PDGFB to primary familial brain calcification and showed the tissue-retention function, not pericyte number alone, underlies the disease.

    Evidence In vitro receptor binding/autophosphorylation of patient mutants, knockout/knockin mouse models, pericyte and BBB readouts; glymphatic CSF-transport analysis

    PMID:26599395 PMID:30865886

    Open questions at the time
    • Mechanism linking retention loss to calcification not fully resolved
    • Glymphatic findings are single-lab Medium confidence
  13. 2023 High

    Cell-source dissection in adults revealed microglia—not endothelium—as the principal PDGFB source maintaining the adult blood-brain barrier, distinguishing developmental from maintenance functions.

    Evidence Transcriptomics/in situ source identification, acute microglial vs endothelial and adult vs neonatal conditional knockouts, BBB integrity and endotoxin-challenge survival; tamoxifen-inducible endothelial knockout comparison with constitutive loss; macrophage- and platelet-derived sources in pulmonary hypertension and tumor metastasis

    PMID:32586981 PMID:33591958 PMID:34689641 PMID:37992789

    Open questions at the time
    • How distinct cellular sources are coordinated in vivo not resolved
    • Signals triggering microglial PDGFB upregulation incompletely defined
  14. 2021 High

    Identifying a microglia→neuronal PDGFRα axis controlling Kv4.3 currents extended PDGFB function beyond mitogenesis to neuronal excitability and blood-pressure control.

    Evidence Microglial ablation, LysM-Cre Pdgfb knockout, neuronal PDGFRα knockdown, electrophysiology, blood pressure measurement, exogenous PDGFB rescue

    PMID:35863346

    Open questions at the time
    • Molecular link between PDGFRα signaling and Kv4.3 expression not defined
    • Single-system finding
  15. 2023 High

    Mapping upstream transcriptional regulators (SDF-1α/ELK-1, E2F1/VEGFR-3, C/EBPβ, PROX1/FOXC2, TIE2/AKT) placed PDGFB within multiple disease-relevant regulatory circuits.

    Evidence ChIP, promoter-reporter, knockdown/overexpression, conditional knockouts, pharmacological rescue, and human tissue validation across pericyte differentiation, vascular malformation, valve degeneration, and cancer contexts

    PMID:21911740 PMID:23633549 PMID:24014887 PMID:34341514 PMID:37555328

    Open questions at the time
    • Cross-talk among these regulators not integrated
    • Several individual circuits are single-lab Medium confidence

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PDGFB integrates its multiple cellular sources, ECM-dependent local retention, and receptor choice (PDGFRβ on mural cells vs PDGFRα on neurons) into context-specific outputs remains unresolved.
  • No unified model of source-specific PDGFB function in vivo
  • Molecular determinant selecting PDGFRα vs PDGFRβ engagement unknown
  • Identity of the SPE/SIF transcription and signaling proteins not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 4 GO:0060089 molecular transducer activity 4
Localization
GO:0005576 extracellular region 3 GO:0005783 endoplasmic reticulum 2 GO:0005794 Golgi apparatus 2 GO:0005886 plasma membrane 2 GO:0031012 extracellular matrix 2
Pathway
R-HSA-74160 Gene expression (Transcription) 6 R-HSA-1643685 Disease 4 R-HSA-1266738 Developmental Biology 3 R-HSA-162582 Signal Transduction 3
Partners
PDGFRAPDGFRB

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1984 The c-sis proto-oncogene encodes a precursor of the B chain of platelet-derived growth factor (PDGF-B), as established by amino acid sequence identity between PDGF B chain and the predicted protein from c-sis genomic sequences over 109 residues. Amino acid sequence analysis of purified PDGF B chain combined with nucleotide sequence analysis of c-sis genomic clones The EMBO journal High 6329745
1984 SSV-transformed cells secrete a PDGF-like protein (p28v-sis or its processed product) that stimulates autocrine cell growth through cell-surface PDGF receptors; anti-PDGF antisera block DNA synthesis in growing SSV-transformed cells and SSV-transformed cells have reduced numbers of high-affinity PDGF receptors; purified PDGF receptor from SSV cells retains active protein tyrosine kinase activity stimulated by PDGF. Mitogenic assays, 125I-PDGF receptor competition binding, anti-PDGF antisera inhibition of 3H-thymidine incorporation, receptor purification with tyrosine kinase activity assay Cell High 6091918
1985 The v-sis gene product transforms cells by binding to PDGF receptors, stimulating tyrosine phosphorylation of PDGF receptors, and inducing DNA synthesis; transformation susceptibility strictly correlates with the presence of PDGF receptors on the target cell; antibodies to different regions of the v-sis product specifically inhibit each of these activities. Partial purification of v-sis protein, PDGF receptor binding assay, tyrosine phosphorylation assay, DNA synthesis induction, antibody inhibition, viral infection of receptor-positive vs. receptor-negative cell types Science High 2996133
1986 The v-sis gene product is processed through the endoplasmic reticulum-Golgi compartment where signal sequence cleavage and N-linked glycosylation occur; the protein contains no transmembrane regions (fully protected from trypsin within microsomes); site-directed mutagenesis of the signal sequence produces proteins with nuclear mislocalization and loss of biological activity; mutagenesis of the proteolytic processing site (Lys-Arg 110-111 to Asn-Ser) retains full biological activity. Site-directed mutagenesis, intracellular fractionation, trypsin protection assay of isolated microsomes, indirect immunofluorescence, biological transformation assay Molecular and cellular biology High 3537701
1986 Transmembrane (membrane-anchored) forms of the v-sis gene product are transported to the cell surface, dimerize, are glycosylated, and undergo NH2-terminal proteolytic processing; removal of the N-linked glycosylation site does not prevent cell surface transport; membrane-anchored mutants retain focus-forming (transforming) activity. Gene fusion construction, indirect immunofluorescence, focus formation assay, N-glycosylation site mutagenesis The Journal of cell biology Medium 3536965
1988 Autocrine stimulation by v-sis (PDGF-B-related protein) requires a ligand-receptor interaction at the cell surface: monensin (blocking secretory transport) and suramin (blocking cell-surface receptor binding) each prevent PDGF receptor autophosphorylation and c-fos induction triggered by v-sis expression, indicating the active signaling event occurs at the plasma membrane rather than intracellularly. Inducible v-sis expression (heat-shock promoter), PDGF receptor autophosphorylation assay, c-fos induction assay, monensin and suramin pharmacological inhibition The Journal of cell biology High 2455725
1989 Transformation by v-sis occurs through an internal autoactivation mechanism: a v-sis mutant targeted for retention in the ER/Golgi (non-secreted) transforms NRK cells as efficiently as wild-type v-sis, and anti-PDGF antisera do not reverse transformation of SSV-NRK cells, demonstrating that intracellular (pre-surface) activation of the PDGF receptor is sufficient for transformation. ER-retention signal mutagenesis of v-sis, focus formation/transformation assay, anti-PDGF antisera treatment of transformed cells, secretion assay Science High 2551043
1989 The 5' untranslated region of c-sis mRNA (1028 nt) contains sequences that inhibit protein synthesis; deletion of nucleotides 154-378 or 398-475 relieves this inhibition; sequences within 375 nt upstream of the RNA initiation site control transcriptional activity, and a transcriptional enhancer within this region is orientation-independent and responds to the HTLV-I transactivator protein. Deletion mutagenesis of 5'UTR in translation assays, CAT reporter gene transcriptional assays, HTLV-I transactivator co-transfection Nucleic acids research Medium 2740212
1989 c-sis mRNA expression in glioblastoma cells is induced by phorbol ester (PMA) and TGF-β1 via transcriptional mechanisms (confirmed by nuclear run-on); PMA induction is protein-kinase C (PKC)-dependent while TGF-β1 induction is PKC-independent; both pathways are blocked by the protein kinase inhibitor H7, implicating a non-PKC kinase in TGF-β1 signaling to c-sis. Nuclear run-on transcription assay, PKC down-regulation, cycloheximide treatment, kinase inhibitors (H7), RNA-RNA solution hybridization Cancer research Medium 2655888
1990 PDGF-B/sis induces a DNA-binding protein (SIF, sis-inducible factor) that binds a conserved element (SIF binding element, ~-100 to -57 of c-fos) and confers PDGF-B-specific transcriptional inducibility on the c-fos promoter; this element functions independently of the serum-responsive element (SRE) and responds only to sis/PDGF (not to serum or phorbol esters); SRE and SIF elements act additively. Conditioned medium and recombinant PDGF-B induction, gel mobility-shift/DNA binding assays, oligonucleotide competition, promoter-reporter transfection with deletion/mutation analysis The EMBO journal High 2176154
1986 Phorbol ester (TPA) induces c-sis transcription in the K-562 hematopoietic stem cell line (megakaryoblastic differentiation), as demonstrated by nuclear run-off transcriptional assay; this induction is not a general effect of TPA on hematopoietic cells. Northern blot analysis, nuclear run-off transcriptional assay, TPA treatment of multiple hematopoietic cell lines Molecular and cellular biology Medium 3466024
1993 A 10-bp element (SIS proximal element, SPE) at positions -58 to -39 relative to the PDGFB mRNA initiation site is essential for TPA-induced transcriptional activation of PDGFB in megakaryocytes; TPA treatment induces formation of a new nuclear protein complex on the SPE that coincides temporally with endogenous PDGFB mRNA induction; both are blocked by cycloheximide, indicating a requirement for new protein synthesis. Linker-scanning mutagenesis of PDGFB promoter, luciferase reporter assay, gel mobility-shift assay with K562 nuclear extracts, cycloheximide inhibition, TPA induction time course Proceedings of the National Academy of Sciences of the United States of America High 8356057
1994 Selective PDGF receptor kinase inhibitors (tyrphostins AG1295 and AG1296) reverse the transformed phenotype of sis-transfected NIH 3T3 cells but have no effect on src-transformed cells, confirming that sis-driven transformation is mediated specifically through PDGF receptor kinase activity. Tyrphostin treatment of sis-transfected NIH 3T3 cells (phenotypic reversion assay), autophosphorylation assays for PDGF-Rα/β, KDR, and c-Src, DNA synthesis assays Cancer research High 7954456
1998 In dermatofibrosarcoma protuberans (DFSP) and giant-cell fibroblastomas, COL1A1-PDGFB chimeric genes always include exon 2 of PDGFB fused to varying exons of COL1A1's alpha-helical domain, placing PDGFB under the COL1A1 promoter and removing negative regulatory elements of PDGFB; retention of exon 2 in all fusions suggests it is required for normal PDGFB polypeptide processing. RT-PCR and DNA sequence analysis of chimeric transcripts from 16 DFSP/GCF tumors, Southern blotting, breakpoint mapping Genes, chromosomes & cancer Medium 9739023
2001 The COL1A1-PDGFB chimeric protein is processed in transfected cells into mature PDGFB dimers; stable expression of COL1A1-PDGFB confers growth factor independence and tumorigenicity in nude mice; conditioned medium stimulates fibroblast growth through PDGFB receptor activation; uncleaved COL1A1-PDGFB forms are also mitogenic, indicating both processed and unprocessed forms contribute to transformation. Stable and transient transfection of chimeric cDNA in PS200 and HEK293 cells, anti-PDGFB and anti-COL1A1-PDGFB antibody immunodetection, PDGFB receptor pathway activation assay, nude mouse tumorigenicity assay, mutagenesis of proteolytic cleavage site Oncogene High 11420709
2001 STI571 (imatinib) inhibits the PDGFB autocrine loop driven by COL1A1-PDGFB, reducing growth and reversing the transformed phenotype of COL1A1-PDGFB-expressing cells in vitro and slowing pre-existing tumor growth in vivo; effects are cytostatic (reversible) rather than cytotoxic, unlike the cytotoxic effect on BCR-ABL tumors. STI571 treatment of 5A cell line (COL1A1-PDGFB transfectants), in vitro growth and morphology assay, nude mouse xenograft tumor growth assay, inhibitor washout reversal experiment International journal of cancer Medium 11291071
2005 PDGF-B signaling induces cytoplasmic relocalization (nuclear-to-cytoplasmic shuttling) and upregulation of Y-box protein 1 (YB-1) in mesangial cells via the MAPK pathway; RNAi knockdown of YB-1 abolishes the mitogenic effect of PDGF-B, establishing YB-1 as a necessary downstream mediator of PDGF-B-driven mesangial cell proliferation. PDGF-B infusion in vivo, anti-Thy1.1 nephritis model, PDGF aptamer and MEK inhibitor (U0126) treatment, YB-1 immunolocalization, RNAi knockdown with proliferation assay Journal of the American Society of Nephrology Medium 16093451
2011 SDF-1α induces PDGF-B expression transcriptionally through the ELK-1 transcription factor binding to the pdgf-b promoter; increased PDGF-B in turn drives differentiation of PDGFR-β+ bone marrow cells into pericytes, establishing SDF-1α→ELK-1→PDGF-B as a pathway controlling pericyte differentiation. PDGF-B mRNA/protein measurement in vitro and in vivo after SDF-1α stimulation, cloning of 2-kb pdgf-b promoter with reporter assay, chromatin immunoprecipitation (ChIP) for ELK-1, in vitro pericyte differentiation assay Molecular cancer research Medium 21911740
2013 TIE2 mutations causing venous malformations reduce PDGFB production in endothelial cells through chronic, ligand-independent AKT activation; reduced PDGFB secretion is demonstrated both in vitro and ex vivo in patient tissues, providing a mechanism for the paucity of vascular smooth muscle cells in these lesions. Global gene expression profiling of TIE2-mutant ECs, PDGFB mRNA/protein quantification in vitro and ex vivo, AKT pathway inhibition rescue experiment Human molecular genetics Medium 23633549
2015 All six analyzed PDGFB loss-of-function mutations causing primary familial brain calcification (PFBC) abolish PDGF-B function either by preventing protein synthesis or by defective binding/stimulation of PDGF-Rβ; Pdgfbret/ret mice (lacking proteoglycan-binding retention motif) develop brain calcifications despite higher pericyte coverage in calcification-prone regions, implicating the tissue-retention function of PDGF-B rather than simple pericyte deficit. In vitro functional analysis of PDGFB mutants (receptor binding and autophosphorylation assays), mouse knockout and knockin models (Pdgfbret/ret), pericyte coverage quantification, BBB permeability assay PloS one High 26599395
2017 PDGFB secreted by lymphatic endothelial cells (LECs) of collecting vessels is required for smooth muscle cell (SMC) recruitment to lymphatic vessels; LEC-specific deletion of Pdgfb prevents SMC investment, causing dilation and loss of pulsatile contraction without affecting vessel identity; PDGFB extracellular matrix retention (via its ECM-binding motif) is required for SMC recruitment, as overexpression in LECs fails to induce SMC coverage of capillaries where PDGFB-binding ECM components are scarce. LEC-specific Pdgfb conditional knockout mice, PDGFB overexpression in LECs, vessel morphology and pulsatile contraction analysis, ECM retention mutant analysis Development High 28851707
1994 PDGF-B (via v-sis) induces Egr-1 expression through a pathway involving tyrosine kinase activity and c-Ha-Ras signaling: dominant-negative Ras and Raf abolish Egr-1 induction by v-sis; the pathway is independent of PKC; Egr-1 promoter activity is stimulated by both v-sis and activated Ras but not by constitutively active Ras. Inducible v-sis NIH3T3 cells (metallothionein promoter), dominant-negative Ras and Raf mutant co-transfection, Egr-1 promoter-reporter assay, Zn2+ dose-response Journal of cellular biochemistry Medium 7890805
2019 PDGF-B deficiency (Pdgfbret/ret mouse, loss of proteoglycan-binding retention motif) suppresses glymphatic system development; formation of astrocytic endfeet and polarized AQP4 expression coincides with the emergence of perivascular CSF transport, and PDGF-B is required for this developmental process. Pdgfbret/ret mouse model, CSF tracer injection/imaging of perivascular transport, AQP4 polarization immunostaining, developmental time-course analysis Cell reports Medium 30865886
2020 Platelet-specific conditional knockout of PDGFB impairs pericyte coverage and tumor vascular function, increases hypoxia and EMT in primary tumors, elevates circulating tumor cells, and increases spontaneous metastasis, establishing platelet-derived PDGFB as a source that maintains vascular integrity via pericyte recruitment in tumors. Platelet-specific conditional Pdgfb knockout mice, tumor pericyte coverage quantification, tumor vascular function assays, circulating tumor cell measurement, spontaneous metastasis assay in two mouse models Cancer research High 32586981
2021 Microglia constitutively release PDGFB, which signals via PDGFRα on hypothalamic pre-sympathetic neurons to promote Kv4.3 (potassium channel) expression; ablation of microglia or microglial-specific deletion of Pdgfb reduces neuronal Kv4.3, increases neuronal excitability and sympathetic outflow, causing hypertension; central PDGFB supplementation suppresses hypertensive responses. Microglial ablation, LysM-Cre conditional Pdgfb knockout, neuronal PDGFRα knockdown in PVN, electrophysiology, Kv4.3 expression analysis, blood pressure measurement, exogenous PDGFB infusion Immunity High 35863346
2021 Macrophage-derived PDGF-B mediates hypoxia-induced distal arteriole muscularization (SMC accumulation) in pulmonary hypertension; hypoxia-inducible factors (HIF-1α/HIF-2α) in macrophages drive Pdgfb upregulation; LysM-Cre conditional deletion of macrophage Pdgfb reduces muscularization and PH; nanoparticle siRNA delivery targeting lung macrophage Pdgfb prevents PH. Clodronate macrophage depletion, LysM-Cre conditional HIF-1α, HIF-2α, and Pdgfb knockout mice, VHL knockout (HIF gain-of-function) mouse, macrophage-conditioned medium SMC proliferation/migration assay, nanoparticle siRNA delivery, right heart catheterization JCI insight High 33591958
2021 Adult-induced endothelial deletion of Pdgfb causes slowly progressing pericyte loss (~50% endothelial:pericyte ratio decrease at 12-18 months) with increased BBB permeability; unlike constitutive loss, adult-induced loss does not cause vessel dilation, arterio-venous skewing, or microvascular calcifications, establishing that developmental vs. maintenance roles of PDGFB are distinct. Tamoxifen-inducible endothelial Cre Pdgfb conditional knockout (2-month-old mice), longitudinal pericyte coverage quantification, BBB permeability assay, vessel morphology analysis, comparison with constitutive Pdgfb knockout Journal of cerebral blood flow and metabolism High 34689641
2023 In adult mice, microglia (not endothelial cells) are the primary source of PDGFB for BBB maintenance; acute deletion of microglial PDGFB profoundly impairs adult BBB integrity and causes fatal microhemorrhages after sublethal endotoxin challenge, while acute abrogation of endothelial PDGFB has minimal adult BBB effect but severely impairs neonatal CNS vasculature; microglia upregulate PDGFB in response to various BBB insults. Transcriptomic analysis and in situ hybridization for PDGFB source identification, acute microglial Pdgfb conditional knockout, acute endothelial Pdgfb conditional knockout in adults and neonates, BBB integrity assay, endotoxin challenge survival assay Brain, behavior, and immunity High 37992789
2013 E2F1 transcriptionally activates PDGF-B expression through a positive feedback loop with VEGF-C/VEGFR-3: E2F1 or VEGFR-3 knockdown reduces PDGF-B levels, while coexpression of E2F1 and VEGFR-3 synergistically upregulates PDGF-B promoter activity and endogenous protein expression. E2F1 forced expression and knockdown, VEGFR-3 knockdown, PDGF-B promoter-reporter assay, Western blot for endogenous PDGF-B, in vivo neovascularization assay in mice Journal of molecular cell biology Medium 24014887
2023 PROX1 transcriptionally represses PDGF-B expression in valvular endothelial cells partly via FOXC2; conditional deletion of Prox1 in VECs upregulates PDGF-B and PDGF-B overexpression in VECs recapitulates myxomatous valve degeneration; pharmacological inhibition of PDGF-B signaling with imatinib partially rescues the Prox1 knockout valve phenotype. Conditional Prox1 knockout in VECs, conditional FOXC2 knockdown, conditional PDGF-B overexpression in VECs, echocardiography, histology, imatinib pharmacological rescue, RNAScope, human mitral valve prolapse sample analysis Circulation research High 37555328
2021 C/EBPβ directly binds to and transactivates the PDGFB promoter in anoikis-resistant gastric cancer cells, increasing PDGFB secretion; secreted PDGFB promotes survival of detached cancer cells via a C/EBPβ-dependent self-feedback loop (autocrine) and promotes angiogenesis via activation of MAPK/ERK signaling in vascular endothelial cells (paracrine). PDGFB promoter ChIP and transcription assay with C/EBPβ, PDGFB secretion quantification, autocrine survival assay in suspension, paracrine endothelial MAPK/ERK activation assay, in vivo peritoneal metastasis models Oncogene Medium 34341514
1999 Cyclic mechanical strain increases PDGF-B mRNA and PDGFB promoter activity (~12-fold) and PDGF-β receptor protein (~1.8-fold) in vascular smooth muscle cells; neutralizing antibodies to the PDGF-β receptor reduce strain-induced DNA synthesis by 50%, establishing PDGF-B as a mediator of mechanically induced VSMC proliferation. Cyclic strain apparatus, PDGFB-promoter-CAT reporter transfection, Northern blot, PDGF-β receptor protein immunoblot, neutralizing antibody inhibition of 3H-thymidine incorporation Biochemical and biophysical research communications Medium 10558917

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Critical care medicine 4335 12682500
2003 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Intensive care medicine 1678 12664219
1990 The SIF binding element confers sis/PDGF inducibility onto the c-fos promoter. The EMBO journal 595 2176154
1984 The c-sis gene encodes a precursor of the B chain of platelet-derived growth factor. The EMBO journal 355 6329745
1984 Transforming protein of simian sarcoma virus stimulates autocrine growth of SSV-transformed cells through PDGF cell-surface receptors. Cell 267 6091918
1994 Selective platelet-derived growth factor receptor kinase blockers reverse sis-transformation. Cancer research 249 7954456
1984 Expression of the sis gene by endothelial cells in culture and in vivo. Proceedings of the National Academy of Sciences of the United States of America 230 6208557
2006 Liver fibrosis induced by hepatic overexpression of PDGF-B in transgenic mice. Journal of hepatology 206 16842882
1989 Transformation by v-sis occurs by an internal autoactivation mechanism. Science (New York, N.Y.) 184 2551043
1985 Evidence that the v-sis gene product transforms by interaction with the receptor for platelet-derived growth factor. Science (New York, N.Y.) 132 2996133
1998 Various regions within the alpha-helical domain of the COL1A1 gene are fused to the second exon of the PDGFB gene in dermatofibrosarcomas and giant-cell fibroblastomas. Genes, chromosomes & cancer 128 9739023
2019 PDGF-B Is Required for Development of the Glymphatic System. Cell reports 116 30865886
1986 Phorbol ester induces c-sis gene transcription in stem cell line K-562. Molecular and cellular biology 116 3466024
2016 PDGF-A and PDGF-B induces cardiac fibrosis in transgenic mice. Experimental cell research 96 27816607
2013 Venous malformation-causative TIE2 mutations mediate an AKT-dependent decrease in PDGFB. Human molecular genetics 91 23633549
2013 Biochemical and biomechanical characterization of porcine small intestinal submucosa (SIS): a mini review. International journal of burns and trauma 88 24273692
2001 Growth-inhibitory effect of STI571 on cells transformed by the COL1A1/PDGFB rearrangement. International journal of cancer 88 11291071
2015 Brain calcification process and phenotypes according to age and sex: Lessons from SLC20A2, PDGFB, and PDGFRB mutation carriers. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 86 26129893
2021 Anoikis resistant gastric cancer cells promote angiogenesis and peritoneal metastasis through C/EBPβ-mediated PDGFB autocrine and paracrine signaling. Oncogene 83 34341514
2015 Functional Characterization of Germline Mutations in PDGFB and PDGFRB in Primary Familial Brain Calcification. PloS one 82 26599395
2004 Angiopoietin 1, PDGF-B, and TGF-beta gene regulation in endothelial cell and smooth muscle cell interaction. Journal of cellular biochemistry 81 14755687
2001 Structural and functional analysis of a chimeric protein COL1A1-PDGFB generated by the translocation t(17;22)(q22;q13.1) in Dermatofibrosarcoma protuberans (DP). Oncogene 77 11420709
2020 Platelet-Specific PDGFB Ablation Impairs Tumor Vessel Integrity and Promotes Metastasis. Cancer research 72 32586981
2003 Cryopreservation of goat oocytes and in vivo derived 2- to 4-cell embryos using the cryoloop (CLV) and solid-surface vitrification (SSV) methods. Theriogenology 69 12566156
2018 Alternative PDGFD rearrangements in dermatofibrosarcomas protuberans without PDGFB fusions. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 68 29955147
2020 An intestinal model with a finger-like villus structure fabricated using a bioprinting process and collagen/SIS-based cell-laden bioink. Theranostics 65 32194815
1988 Autocrine stimulation by the v-sis gene product requires a ligand-receptor interaction at the cell surface. The Journal of cell biology 63 2455725
2010 Expression of platelet-derived growth factor (PDGF)-B and PDGF-receptor β is associated with lymphatic metastasis in human gastric carcinoma. Cancer science 61 20624165
2006 Gains of COL1A1-PDGFB genomic copies occur in fibrosarcomatous transformation of dermatofibrosarcoma protuberans. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 61 16980946
2021 Macrophage-derived PDGF-B induces muscularization in murine and human pulmonary hypertension. JCI insight 59 33591958
2018 SIS-ECM Laden with GMSC-Derived Exosomes Promote Taste Bud Regeneration. Journal of dental research 59 30335555
1985 Translocation of oncogene c-sis from chromosome 22 to chromosome 11 in a Ewing sarcoma-derived cell line. Molecular and cellular biology 59 2983195
2013 E2F1 promotes angiogenesis through the VEGF-C/VEGFR-3 axis in a feedback loop for cooperative induction of PDGF-B. Journal of molecular cell biology 58 24014887
2007 Detection of COL1A1-PDGFB fusion transcripts and PDGFB/PDGFRB mRNA expression in dermatofibrosarcoma protuberans. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 56 17431412
2017 Smooth muscle cell recruitment to lymphatic vessels requires PDGFB and impacts vessel size but not identity. Development (Cambridge, England) 55 28851707
2015 PDGFB-based stem cell gene therapy increases bone strength in the mouse. Proceedings of the National Academy of Sciences of the United States of America 54 26150503
2013 LIM-homeobox gene 2 promotes tumor growth and metastasis by inducing autocrine and paracrine PDGF-B signaling. Molecular oncology 54 24423492
2022 Microglia-derived PDGFB promotes neuronal potassium currents to suppress basal sympathetic tonicity and limit hypertension. Immunity 51 35863346
2014 PDGFB partial deletion: a new, rare mechanism causing brain calcification with leukoencephalopathy. Journal of molecular neuroscience : MN 50 24604296
2021 Adult-induced genetic ablation distinguishes PDGFB roles in blood-brain barrier maintenance and development. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 47 34689641
2014 A de novo nonsense PDGFB mutation causing idiopathic basal ganglia calcification with laryngeal dystonia. European journal of human genetics : EJHG 44 24518837
1999 Mechanical strain increases PDGF-B and PDGF beta receptor expression in vascular smooth muscle cells. Biochemical and biophysical research communications 44 10558917
1990 Enhanced expression of the sis and c-myc oncogenes in human meningiomas. Journal of neurosurgery 43 2182793
2018 Nanosphere-mediated co-delivery of VEGF-A and PDGF-B genes for accelerating diabetic foot ulcers healing in rats. Gene therapy 42 29955127
2019 Spectrum of SLC20A2, PDGFRB, PDGFB, and XPR1 mutations in a large cohort of patients with primary familial brain calcification. Human mutation 41 30609140
1995 scute (sis-b) function in Drosophila sex determination. Molecular and cellular biology 41 7623836
2009 VEGF-C regulates lymphangiogenesis and capillary stability by regulation of PDGF-B. American journal of physiology. Heart and circulatory physiology 40 19734356
2005 Y-box protein 1 mediates PDGF-B effects in mesangioproliferative glomerular disease. Journal of the American Society of Nephrology : JASN 40 16093451
2000 Effects of H-ras and v-sis overexpression on N-acetylglucosaminyltransferase V and metastasis-related phenotypes in human hepatocarcinoma cells. Journal of cancer research and clinical oncology 40 10815761
1989 Regulation of expression of the c-sis proto-oncogene. Nucleic acids research 40 2740212
1989 Control of the expression of c-sis mRNA in human glioblastoma cells by phorbol ester and transforming growth factor beta 1. Cancer research 39 2655888
1986 C-sis and C-abl expression in chronic myelogenous leukemia and other hematologic malignancies. Blood 38 3456250
2013 Lrig2-deficient mice are protected against PDGFB-induced glioma. PloS one 37 24023893
2009 Short-term plasticity of small synaptic vesicle (SSV) and large dense-core vesicle (LDCV) exocytosis. Cellular signalling 37 19249357
1988 Kidney epithelial cells express c-sis protooncogene and secrete PDGF-like protein. The American journal of physiology 35 3177660
2019 SPARC promotes the proliferation and metastasis of oral squamous cell carcinoma by PI3K/AKT/PDGFB/PDGFRβ axis. Journal of cellular physiology 33 30706473
2001 Expression of COL1A1-PDGFB fusion transcripts in superficial adult fibrosarcoma suggests a close relationship to dermatofibrosarcoma protuberans. The Journal of pathology 32 11329146
1990 Induction of fos and sis proto-oncogenes and genes of the extracellular matrix proteins during butyrate induced glioma differentiation. Biochimica et biophysica acta 32 2105102
2011 SDF-1α induces PDGF-B expression and the differentiation of bone marrow cells into pericytes. Molecular cancer research : MCR 31 21911740
2021 M2 Macrophages Promote PDGFRβ+ Pericytes Migration After Spinal Cord Injury in Mice via PDGFB/PDGFRβ Pathway. Frontiers in pharmacology 30 33935795
1993 Identification and characterization of an essential, activating regulatory element of the human SIS/PDGFB promoter in human megakaryocytes. Proceedings of the National Academy of Sciences of the United States of America 30 8356057
1988 Expression and stability of c-sis mRNA in human glioblastoma cells. Biochemistry 30 3052584
2020 Endothelial Twist1-PDGFB signaling mediates hypoxia-induced proliferation and migration of αSMA-positive cells. Scientific reports 29 32371931
2015 PDGF-D signaling in portal myofibroblasts and hepatic stellate cells proves identical to PDGF-B via both PDGF receptor type α and β. Cellular signalling 29 25819339
2022 Platelet-Derived PDGFB Promotes Recruitment of Cancer-Associated Fibroblasts, Deposition of Extracellular Matrix and Tgfβ Signaling in the Tumor Microenvironment. Cancers 28 35454853
2020 MicroRNA-29b-3p inhibits cell proliferation and angiogenesis by targeting VEGFA and PDGFB in retinal microvascular endothelial cells. Molecular vision 27 32165827
2020 Effect of PDGF-B Gene-Activated Acellular Matrix and Mesenchymal Stem Cell Transplantation on Full Thickness Skin Burn Wound in Rat Model. Tissue engineering and regenerative medicine 27 33145744
1998 COL1A1-PDGFB fusion in a ring chromosome 4 found in a dermatofibrosarcoma protuberans. Genes, chromosomes & cancer 27 9790508
1986 Cell surface expression of membrane-anchored v-sis gene products: glycosylation is not required for cell surface transport. The Journal of cell biology 27 3536965
1986 Biosynthesis of the v-sis gene product: signal sequence cleavage, glycosylation, and proteolytic processing. Molecular and cellular biology 26 3537701
2023 New Insights into Baicalein's Effect on Chlorpyrifos-Induced Liver Injury in Carp: Involving Macrophage Polarization and Pyropto sis. Journal of agricultural and food chemistry 25 36848483
2019 PDGFB-expressing mesenchymal stem cells improve human hematopoietic stem cell engraftment in immunodeficient mice. Bone marrow transplantation 25 31804621
2018 Effect of PDGF-B aptamer on PDGFRβ/PDGF-B interaction: Molecular dynamics study. Journal of molecular graphics & modelling 25 29738888
2005 Hypoxia regulates PDGF-B interactions between glomerular capillary endothelial and mesangial cells. Kidney international 24 16014047
2007 Induction of PDGF-B in TCA-treated epidermal keratinocytes. Archives of dermatological research 23 17724602
2013 PDGFB rearrangement in dermatofibrosarcoma protuberans: correlation with clinicopathologic characteristics and clinical implications. Human pathology 22 23347652
1986 Structure and nucleotide sequence of the 5' region of the human and feline c-sis proto-oncogenes. Nucleic acids research 22 3003695
2022 PDGFB targeting biodegradable FePt alloy assembly for MRI guided starvation-enhancing chemodynamic therapy of cancer. Journal of nanobiotechnology 21 35672821
2021 MicroRNA-432-5p regulates sprouting and intussusceptive angiogenesis in osteosarcoma microenvironment by targeting PDGFB. Laboratory investigation; a journal of technical methods and pathology 21 33846539
2019 SIS/aligned fibre scaffold designed to meet layered oesophageal tissue complexity and properties. Acta biomaterialia 20 31446049
1994 Specific inhibition of c-sis protein synthesis and cell proliferation with antisense oligodeoxynucleotides in human glioma cells. Neurosurgery 20 8177392
2021 PDGFB RNA in situ hybridization for the diagnosis of dermatofibrosarcoma protuberans. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 19 33762682
1990 S71 is a phylogenetically distinct human endogenous retroviral element with structural and sequence homology to simian sarcoma virus (SSV). Virology 19 2152993
2023 An integral blood-brain barrier in adulthood relies on microglia-derived PDGFB. Brain, behavior, and immunity 18 37992789
2007 Study of biocompatibility of small intestinal submucosa (SIS) with Schwann cells in vitro. Brain research 18 17367764
2022 Endothelial senescence mediates hypoxia-induced vascular remodeling by modulating PDGFB expression. Frontiers in medicine 17 36203755
2021 Overexpression of MiR-29b-3p Inhibits Atrial Remodeling in Rats by Targeting PDGF-B Signaling Pathway. Oxidative medicine and cellular longevity 17 33520084
2019 Genomic and transcriptomic features of dermatofibrosarcoma protuberans: Unusual chromosomal origin of the COL1A1-PDGFB fusion gene and synergistic effects of amplified regions in tumor development. Cancer genetics 17 31870844
2018 200+ Protein Concentrations in Healthy Human Blood Plasma: Targeted Quantitative SRM SIS Screening of Chromosomes 18, 13, Y, and the Mitochondrial Chromosome Encoded Proteome. Journal of proteome research 17 30480452
1987 Platelet-derived growth factor/sis in normal and neoplastic cell growth. Journal of cellular physiology. Supplement 17 2824537
2023 PROX1 Inhibits PDGF-B Expression to Prevent Myxomatous Degeneration of Heart Valves. Circulation research 16 37555328
2022 Intratumoral PDGFB gene predominantly expressed in endothelial cells is associated with angiogenesis and lymphangiogenesis, but not with metastasis in breast cancer. Breast cancer research and treatment 16 35793004
1977 Establishment of simian sarcoma virus, type 1 (SSV-1)-transformed non-producer marmoset cell lines. International journal of cancer 16 198378
2005 The effect of equilibration time on survival and development rates of mouse pronuclear-stage embryos vitrified in solid surface (SSV) and convential straws: in vitro and in vivo evaluations. Molecular reproduction and development 15 16110514
1992 Expression of c-sis and c-fos genes in human meningiomas and neurinomas. International journal of cancer 15 1353485
1989 Expression of c-sis and other cellular proto-oncogenes in human sarcoma cell lines and biopsies. International journal of cancer 15 2793239
2022 SB431542 alleviates lupus nephritis by regulating B cells and inhibiting the TLR9/TGFβ1/PDGFB signaling. Journal of autoimmunity 14 36030617
1994 V-sis induces Egr-1 expression by a pathway mediated by c-Ha-Ras. Journal of cellular biochemistry 14 7890805
2022 Diverse roles of tumor-stromal PDGFB-to-PDGFRβ signaling in breast cancer growth and metastasis. Advances in cancer research 13 35459473
1985 Platelet-derived growth factor: roles in normal and v-sis transformed cells. Cancer surveys 13 2824043

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