Affinage

PTN

Pleiotrophin · UniProt P21246

Length
168 aa
Mass
18.9 kDa
Annotated
2026-04-28
78 papers in source corpus 25 papers cited in narrative 25 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PTN is a secreted heparin-binding growth factor that signals through multiple cell-surface receptors—principally PTPRZ1/RPTPβ/ζ, ALK, and syndecans (SDC2, SDC4)—to regulate neurite outgrowth, neural stem cell niche signaling, oligodendrocyte differentiation, cell proliferation, and survival across diverse tissues (PMID:2610682, PMID:30497772, PMID:30667096, PMID:39285301). PTN binds and inactivates the phosphatase activity of PTPRZ1, thereby permitting phosphorylation of substrates such as ALK and AFAP1L2 and activating downstream PI3K-AKT, MAPK/ERK, NF-κB, and AMPK-PGC1α cascades that govern context-dependent outcomes including cancer cell chemoresistance, osteogenesis, and cardioprotection (PMID:23077859, PMID:30667096, PMID:30497491, PMID:41640280). Sulfated glycosaminoglycans promote PTN dimerization, and its secretion from oligodendrocyte precursor cells depends on COPII-mediated ER exit via the TRAPPC12–Mea6/cTAGE5 machinery (PMID:10600521, PMID:38439956). In the nervous system, PTN functions as a niche-derived paracrine factor: astrocyte- or neural stem cell-secreted PTN supports hippocampal neurogenesis and newborn neuron dendritic maturation, and dysregulated PTN release from quiescent neural stem cells contributes to manic-like behavioral phenotypes (PMID:30497772, PMID:39729991, PMID:40069581).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1989 High

    Identifying PTN as a distinct heparin-binding mitogen established it as a novel growth factor family member, separate from FGFs, with potent proliferative activity.

    Evidence Purification from bovine uterus with heparin-affinity chromatography, N-terminal sequencing, and ³H-thymidine incorporation assay on NIH 3T3 cells

    PMID:2610682

    Open questions at the time
    • No receptor identified
    • In vivo relevance of mitogenic activity not tested
    • Mechanism of mitogenic signaling unknown
  2. 1991 High

    Full structural characterization of PTN as a 136-amino-acid protein with C-terminal proteolytic processing variants resolved ambiguities about its molecular identity and revealed post-translational regulation.

    Evidence Purification from bovine brain with amino acid sequencing, SDS-PAGE, and composition analysis ± protease inhibitors

    PMID:1700712 PMID:2049182

    Open questions at the time
    • Three-dimensional structure not solved
    • Functional significance of C-terminal truncation unknown
  3. 1999 Medium

    Demonstrating GAG-dependent dimerization of PTN revealed that sulfated glycosaminoglycans are not merely co-receptors but actively modulate PTN oligomeric state and extracellular signaling competence.

    Evidence DSS cross-linking, heparin/dermatan sulfate/CS-C binding assays, chlorate treatment blocking sulfation, conditioned medium analysis

    PMID:10600521

    Open questions at the time
    • Whether dimerization is required for receptor activation not tested
    • Stoichiometry of PTN-GAG complex not determined
    • Crystal structure of dimer not available
  4. 2000 High

    Discovery that a human endogenous retrovirus element (HERV-E.PTN) provides an alternative Sp1-dependent promoter for PTN in trophoblast/choriocarcinoma revealed an evolutionary co-opted regulatory mechanism for tissue-specific expression.

    Evidence Reporter assays, EMSA, ChIP, site-directed mutagenesis of Sp1 site, Drosophila SL2 reconstitution

    PMID:10962555

    Open questions at the time
    • Whether this promoter operates in other cancer types not established
    • Epigenetic regulation of HERV-E.PTN not characterized
  5. 2009 High

    Identification of IFN-γ/JAK/STAT1 as a transcriptional inducer of PTN in macrophages placed PTN within the innate immune signaling network and identified a GAS element in the PTN promoter.

    Evidence JAK inhibitors, STAT1 siRNA, ChIP, EMSA/supershift on the −2086 GAS element in macrophages

    PMID:19917672

    Open questions at the time
    • Downstream function of macrophage-derived PTN not determined
    • Whether STAT1-driven PTN contributes to inflammation in vivo not tested
  6. 2010 Medium

    Placing PTN downstream of menin-mediated transcriptional repression and upstream of RPTPβ/ζ–integrin αvβ3–FAK–PI3K–ERK signaling in lung cancer migration built the first multi-node signaling pathway for PTN in a cancer context.

    Evidence Ectopic menin overexpression, PI3K/FAK inhibitor studies, migration assays in A549 cells

    PMID:20639902

    Open questions at the time
    • Direct menin binding to PTN promoter not shown
    • In vivo relevance in lung cancer not tested
  7. 2012 Medium

    Demonstrating that endogenous PTN signals through ALK to regulate mammary epithelial progenitor maintenance and ductal morphogenesis via ERK1/2 extended PTN's developmental roles beyond the nervous system.

    Evidence Anti-PTN blocking antibody, mammosphere assays, in vivo mammary gland analysis, ERK1/2 phosphorylation

    PMID:23077670

    Open questions at the time
    • Whether ALK or RPTPζ is the dominant receptor in mammary epithelium not resolved
    • PTN knockout mammary phenotype not reported
  8. 2013 Medium

    Mechanistic clarification that PTN activates ALK indirectly—by inactivating RPTPβ/ζ phosphatase activity that normally dephosphorylates ALK—unified the PTN-RPTPζ and PTN-ALK literature into a single signaling axis.

    Evidence Review synthesizing biochemical studies on PTN/RPTPβ/ζ/ALK pathway

    PMID:23777859

    Open questions at the time
    • Direct structural evidence for PTN-induced RPTPζ conformational change not available
    • Quantitative kinetics of RPTPζ inactivation not measured
  9. 2018 High

    Establishing that neural stem cells continuously supply PTN as a paracrine niche signal required for newborn neuron dendritic maturation defined PTN's role in adult hippocampal neurogenesis.

    Evidence Conditional PTN deletion in NSCs, retrovirus single-cell labeling, dendritic morphometry in mouse hippocampus

    PMID:30497772

    Open questions at the time
    • Receptor mediating dendritic maturation effect not identified in this study
    • Whether PTN acts directly on newborn neurons or via intermediate cells not fully resolved
  10. 2019 High

    Identification of AFAP1L2 as a direct PTPRZ substrate and demonstration that PTN-mediated PTPRZ inactivation drives PI3K-AKT-mTOR signaling for OPC differentiation provided the first complete substrate-to-phenotype pathway for PTN-PTPRZ.

    Evidence In vitro phosphatase assay, PTPRZ catalytic-dead (C→S) knock-in mouse, cuprizone demyelination model, PI3K inhibitor

    PMID:30667096

    Open questions at the time
    • Whether AFAP1L2 is the sole PTPRZ substrate relevant to differentiation unknown
    • Human relevance not directly tested
  11. 2024 Medium

    Revealing that PTN secretion from OPCs requires COPII-dependent ER exit controlled by the TRAPPC12–Mea6/cTAGE5 complex defined the intracellular trafficking machinery governing PTN release.

    Evidence Conditional Mea6 knockout in OPCs, TRAPPC12 knockdown, Co-IP for TRAPPC12–Mea6, exogenous PTN rescue of differentiation deficits

    PMID:38439956

    Open questions at the time
    • Whether this trafficking pathway is specific to PTN or shared with other secreted cargoes not determined
    • Direct visualization of PTN in COPII vesicles not shown
  12. 2024 Medium

    Identifying SDC2 as the PTN receptor on spermatogonial stem cells and delineating a PTN-SDC2-GFRA1 axis expanded PTN's paracrine niche functions to the male germline.

    Evidence Co-IP for PTN-SDC2 interaction, SDC2 knockdown, exogenous PTN rescue, transcriptome analysis in human SSC lines

    PMID:39285301

    Open questions at the time
    • In vivo SSC phenotype upon PTN loss not examined
    • Whether SDC2 acts as a co-receptor with PTPRZ1 in SSCs not tested
  13. 2024 Medium

    Demonstrating that astrocyte-derived PTN activates AKT to promote hippocampal neurogenesis and that its loss exacerbates demyelination-induced neurogenic deficits established cell-type-specific PTN sources as critical niche determinants.

    Evidence Astrocyte-specific conditional PTN knockout and overexpression, cuprizone demyelination model, AKT signaling analysis, cognitive behavioral testing

    PMID:39729991

    Open questions at the time
    • Relative contributions of astrocyte vs. NSC-derived PTN to neurogenesis not compared directly
    • Whether PTN acts through PTPRZ1 or ALK in this context not discriminated
  14. 2025 Medium

    Discovery that PTN directly binds SIRT1 and activates AMPK-PGC1α to reprogram mitochondrial metabolism and protect cardiomyocytes from doxorubicin toxicity established a metabolic signaling axis independent of the canonical PTPRZ/ALK receptors.

    Evidence PTN-SIRT1 binding assay, AMPK Thr172 phosphorylation analysis, mitochondrial function assays, in vivo doxorubicin cardiotoxicity model

    PMID:41640280

    Open questions at the time
    • Whether PTN-SIRT1 interaction is direct or mediated by a receptor complex not fully resolved
    • Structural basis of PTN-SIRT1 interaction not characterized
    • Independent replication needed
  15. 2025 Medium

    Linking dysregulated PTN release from quiescent NSCs to aberrant neurogenesis and manic-like behavior in Shank3-overexpressing mice positioned PTN as a mechanistic effector in psychiatric-relevant circuitry.

    Evidence scRNA-seq, conditional Shank3 overexpression, pharmacological and genetic PTN inhibition in qNSCs, behavioral rescue

    PMID:40069581

    Open questions at the time
    • PTN receptor mediating this behavioral phenotype not identified
    • Relevance to human mania not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of PTN-induced PTPRZ1 inactivation, whether dimerization is required for receptor engagement, how receptor selectivity (PTPRZ1 vs. ALK vs. syndecans) is determined in different cellular contexts, and whether intracellular PTN-SIRT1 signaling represents a receptor-independent mechanism.
  • No crystal or cryo-EM structure of PTN-receptor complex
  • No systematic comparison of receptor usage across cell types
  • Physiological importance of C-terminal proteolytic processing uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 8 GO:0098772 molecular function regulator activity 3
Localization
GO:0005576 extracellular region 6
Pathway
R-HSA-112316 Neuronal System 5 R-HSA-1266738 Developmental Biology 4
Partners
AFAP1L2ALKPTPRZ1SDC2SDC4SIRT1

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1989 PTN (designated HBGF-8) was purified to near homogeneity from bovine uterus as a novel 17 kDa heparin-binding growth factor with mitogenic activity on NIH 3T3 fibroblasts, stimulating DNA synthesis at potency comparable to aFGF; its unique N-terminal amino acid sequence distinguished it from bFGF. Protein purification (heparin-Sepharose affinity chromatography, cation exchange), N-terminal amino acid sequencing, 3H-thymidine incorporation mitogenic assay Biochemical and biophysical research communications High 2610682
1991 PTN (HBNF) was purified to homogeneity from bovine brain and structurally characterized as a 136-amino acid protein (~15.5 kDa calculated, ~18 kDa apparent), with C-terminally truncated isoforms identified when protease inhibitors were omitted during extraction, indicating susceptibility to proteolytic processing at the C-terminus. Protein purification (pH 4.5 extraction, ammonium sulfate precipitation, cation exchange, heparin-Sepharose, reverse phase HPLC), amino acid sequencing, SDS-PAGE, amino acid composition analysis Growth factors (Chur, Switzerland) High 2049182
1990 PTN (HBNF) and midkine (MK) were identified as members of a novel family of homologous heparin-binding proteins with ~55% structural homology and complete alignment of 9 cysteine residues, suggesting similar 3D structures; PTN stimulates neurite outgrowth in neurons. cDNA cloning, nucleotide sequencing, amino acid sequence comparison, structural alignment Biochemical and biophysical research communications High 1700712
1999 PTN (HARP) forms noncovalent dimers, and dimerization is promoted by heparin and other sulfated glycosaminoglycans (dermatan sulfate, chondroitin sulfate-C); chlorate treatment of cells (which inhibits sulfation) prevents dimerization, and PTN is secreted as a dimer in conditioned medium of NIH-3T3 cells overexpressing the protein. DSS cross-linking, affinity chromatography, chlorate treatment of cells, conditioned medium analysis Biochemical and biophysical research communications Medium 10600521
2000 A human endogenous retrovirus-like element (HERV-E.PTN) inserted into the PTN gene generates a novel promoter driving HERV-PTN fusion transcripts in choriocarcinoma and trophoblastic tissue; a retroviral Sp1-binding site within an enhancer region (+443 to +486) is essential for PTN expression in choriocarcinoma cells, as shown by site-specific mutation abolishing activity. In situ hybridization, transient transfection reporter assays, deletion analysis, EMSA, supershift assays, chromatin immunoprecipitation, Sp1 overexpression in Drosophila SL2 cells, site-directed mutagenesis Oncogene High 10962555
2009 IFN-γ markedly induces PTN mRNA expression in macrophages via the JAK/STAT1 signaling pathway; STAT1 (but not STAT3 or p42) binds a gamma-activated sequence (GAS) at -2086 to -2078 bp in the PTN promoter at the chromatin level, and siRNA knockdown of STAT1 markedly reduces PTN mRNA levels. Janus kinase inhibitors, STAT1 siRNA knockdown, STAT1/STAT3/p42 phosphorylation analysis, PTN promoter analysis, EMSA, supershift assays, chromatin immunoprecipitation FASEB journal High 19917672
2010 Menin represses PTN transcription, and PTN signals through its receptor RPTP β/ζ together with integrin αvβ3, FAK, PI3K, and phospho-ERK1/2 to regulate lung cancer cell migration; ectopic menin expression reduces RPTP β/ζ expression indirectly through repression of PTN. Ectopic menin overexpression, PTN transcription repression assays, cell migration assays (A549 cells), pathway inhibitor studies (PI3K, FAK), signaling protein analysis Oncogene Medium 20639902
2013 PTN activates ALK through a 'ligand independent' mechanism: PTN binds and inactivates the phosphatase activity of RPTP β/ζ, which normally dephosphorylates phosphotyrosine sites in the ALK activation domain; inactivation of RPTP β/ζ by PTN leads to ALK autophosphorylation and autoactivation. Review synthesizing biochemical pathway studies; mechanism established by referenced primary experiments on PTN/RPTPβ/ζ/ALK signaling Biochimica et biophysica acta Medium 23777859
2014 PTN signals through its receptor PTPRZ1 in epithelial ovarian cancer cells; siRNA-mediated knockdown of PTN or PTPRZ1 induces apoptosis, and expression profiling after PTN silencing identifies MAPK family members as likely effectors of PTN survival signaling in EOC cells. siRNA knockdown of PTN and PTPRZ1, apoptosis assays, 36-gene expression profiling, computational pathway mapping Molecular carcinogenesis Medium 25418856
2019 PTN signals through PTPRZ to promote oligodendrocyte precursor cell (OPC) differentiation via the PI3K-AKT pathway; PTPRZ dephosphorylates AFAP1L2 at tyrosine residues in vitro and in HEK293T cells, and PTN treatment enhances phosphorylation of AFAP1L2, AKT, and mTOR; knockdown of AFAP1L2 or PI3K inhibition suppresses OPC differentiation; knock-in mice with catalytically inactive PTPRZ (Cys→Ser) show accelerated OPC differentiation and earlier remyelination after cuprizone-induced demyelination. In vitro phosphatase assay, HEK293T cell transfection, OL1 cell knockdown, PI3K inhibitor, PTPRZ catalytic dead knock-in mouse, cuprizone demyelination model, western blot, immunostaining Glia High 30667096
2018 Adult hippocampal neural stem cells (NSCs) continuously supply PTN as a feedforward signal to newborn neurons; conditional ablation of PTN in NSCs causes defective dendritic development and arborization of newborn neurons, establishing NSC-derived PTN as a niche factor governing newborn neuron maturation. Cell ablation, retrovirus-mediated single-cell labeling, signaling pathway modulation, conditional PTN deletion in NSCs, morphological analysis of dendritic arborization Neuron High 30497772
2005 JUN (AP-1 subunit) in dermal fibroblasts transcriptionally regulates PTN expression; PTN exerts a mitogenic effect on primary human keratinocytes in a heterologous feeder layer co-culture system; co-cultivation with keratinocytes stimulates PTN expression in fibroblasts, and PTN is upregulated during cutaneous wound healing in vivo. Gene expression profiling of wild-type vs. Jun-/- mouse embryonic fibroblasts, semi-quantitative RT-PCR, in situ hybridization on murine skin sections, heterologous co-culture system, in vivo wound healing model Journal of cell science Medium 15840658
2012 In mammary epithelial cells, endogenous PTN signals through ALK to regulate cell motility, invasion, and progenitor maintenance; blocking endogenous PTN with a monoclonal antibody increases mammosphere formation with laminin deposition and upregulates progenitor markers; in vivo, PTN inhibits ductal outgrowth and branching via inhibition of phospho-ERK1/2 signaling in mammary epithelial cells. Anti-PTN blocking antibody treatment, real-time impedance monitoring, 3D culture mammosphere assay, immunostaining, in vivo mammary gland development analysis, ERK1/2 phosphorylation assay PloS one Medium 23077670
1992 Recombinant PTN (HBNF) inhibits infectivity of herpes simplex virus types 1 and 2 and human cytomegalovirus; carboxymethylated HBNF, which retains heparin-Sepharose affinity, loses antiviral activity, indicating that the antiviral mechanism depends on competition for specific binding to cell surface heparan sulfate proteoglycans. Viral infectivity assays, chemical modification (carboxymethylation) of HBNF, heparin-Sepharose binding assay Biochemical and biophysical research communications Medium 1335242
2018 Chemotherapy drives upregulation of PTN and its receptor PTPRZ1 in triple-negative breast cancer cells via CDKN1A; the CDKN1A/PTN/PTPRZ1 axis promotes chemoresistance by activating the NF-κB pathway, increasing tumor proliferation and inhibiting apoptosis; siRNA knockdown confirmed PTPRZ1 as the downstream effector. Microarray analysis, siRNA knockdown, CCK-8 proliferation assay, colony formation assay, apoptosis analysis, NF-κB pathway analysis Cell communication and signaling Medium 30497491
2011 Adenoviral shRNA-mediated knockdown of PTN in pancreatic cancer BxPC-3 cells reduces PTN mRNA and protein, and co-culture of dorsal root ganglion (DRG) neurons with PTN-depleted BxPC-3 cells results in significant reduction in neurite number and length, demonstrating that tumor cell-derived PTN promotes DRG neurite outgrowth. Adenoviral shRNA knockdown, RT-PCR, immunocytochemistry, Western blotting, DRG co-culture neurite outgrowth assay World journal of gastroenterology Medium 21677838
2024 PTN from Leydig cells binds to its receptor syndecan-2 (SDC2) on spermatogonial stem cells (SSCs); SDC2 knockdown impairs SSC proliferation, DNA synthesis, and PLZF expression, and downregulates GFRA1 and the HIF-1 signaling pathway; exogenous PTN rescues proliferation and GFRA1 expression in SDC2 knockdown SSC lines, establishing the PTN-SDC2-GFRA1 axis in human SSC regulation. Single-cell sequencing analysis, immunofluorescence, STRING prediction, co-immunoprecipitation, SDC2 knockdown, transcriptome analysis, exogenous PTN rescue experiments Biological research Medium 39285301
2025 PTN secreted by cardiac fibroblasts acts on syndecan-4 (SDC4) receptor to promote cardiac fibroblast proliferation/invasion and stimulate macrophage inflammatory responses (TNF-α, IL-6, Cox-2) in pressure overload-induced hypertrophic cardiomyopathy; the PTN-SDC4 pathway was validated both in vitro and in vivo using TAC mouse model. scRNA-seq, CellChat cell-cell interaction analysis, WGCNA, RT-qPCR, EdU staining, transwell assay, western blot, immunofluorescence, TAC mouse model, echocardiography Life sciences Medium 39765325
2025 PTN directly binds SIRT1 and activates AMPK phosphorylation at Thr172, triggering the AMPK-PGC1α axis to reprogram mitochondrial energy metabolism; PTN overexpression reduces oxidative stress and apoptosis in cardiomyocytes and improves cardiac function in a doxorubicin cardiotoxicity model. PTN overexpression in cellular and animal DIC models, western blot, AMPK phosphorylation assay, mitochondrial function assays, PTN-SIRT1 binding assay, in vivo cardiac function assessment Acta biochimica et biophysica Sinica Medium 41640280
2025 PTN binds PTPRZ1 receptor and induces PLCG1 phosphorylation and NCOA3 nuclear translocation to regulate antioxidant functions and reduce ROS in rat bone marrow mesenchymal stem cells, promoting osteogenic differentiation; PTN inhibited apoptosis and enhanced osteogenesis in vitro, and promoted fracture healing in osteoporotic rats in vivo. RT-qPCR, immunofluorescence, ALP detection, TUNEL assay, RNA sequencing, phosphorylation quantitative proteomics, fracture healing in osteoporosis rat model Biomedicines Medium 40149671
2024 Astrocyte-derived PTN promotes hippocampal neurogenesis by cooperating with PTPRZ1 or ALK receptors to activate the AKT signaling pathway; conditional ablation of PTN in astrocytes exacerbates neurogenic deficits in demyelinated hippocampus, while astrocyte-specific PTN overexpression reverses neurogenic and cognitive impairments caused by demyelination. Conditional genetic deletion of PTN in astrocytes, PTN overexpression in astrocytes, demyelination (cuprizone) model, AKT signaling pathway analysis, hippocampal neurogenesis quantification, cognitive behavioral tests Stem cell reports Medium 39729991
2025 In the prostate, androgen receptor (AR) signaling controls epithelial homeostasis partly through a stromal signal mediated by secreted PTN; castration-induced ferroptosis in prostate epithelium is regulated by PTN as an extrinsic stromal pathway (alongside an intrinsic NKX3.1-dependent pathway), with PTN signaling coordinating monounsaturated fatty acid phospholipid biosynthesis and GPX4 expression to suppress ferroptosis. Genetically engineered mouse models, human organotypic cultures, castration experiments, in vivo analysis of AR signaling pathways, lipid and GPX4 expression analysis bioRxivpreprint Medium bio_10.1101_2025.08.06.668974
2024 PTN secretion from oligodendrocyte precursor cells (OPCs) is regulated by TRAPPC12 and Mea6/cTAGE5 via COPII-dependent ER exit; Mea6/cTAGE5 ablation in OPCs disrupts PTN secretion, and exogenous PTN supplementation ameliorates OPC differentiation deficits, demonstrating PTN acts as a secreted factor downstream of the Mea6/TRAPPC12 trafficking machinery to support white matter development. Conditional knockout of Mea6/cTAGE5 in OPCs, TRAPPC12 knockdown in CG4/OPC cells, co-immunoprecipitation (TRAPPC12-Mea6 interaction), PTN secretion measurement, exogenous PTN rescue experiment, OPC differentiation assays, behavioral phenotyping iScience Medium 38439956
2025 PTN released by dysregulated quiescent neural stem cells (qNSCs) is a key factor contributing to manic-like phenotypes in Shank3-overexpressing mice; pharmacological and molecular inhibition of PTN in qNSCs rescued aberrant neurogenesis and alleviated manic-like social deficits, placing PTN downstream of Shank3 overexpression in qNSCs. scRNA-seq analysis, conditional Shank3 overexpression mouse model, pharmacological PTN inhibition, molecular (genetic) PTN inhibition in qNSCs, neurogenesis quantification, behavioral assays Nature communications Medium 40069581
2014 CART neuropeptide facilitates neurite outgrowth in cortical neurons after oxygen-glucose deprivation (OGD) through a PTN-dependent pathway; siRNA-mediated PTN knockdown abolishes CART-stimulated increases in GAP43 protein levels, placing PTN as a required downstream mediator of CART neuroprotective signaling. Primary cortical neuron OGD model, siRNA knockdown of PTN, western blot for GAP43, flow cytometry for apoptosis Neuroscience Low 25010400

Source papers

Stage 0 corpus · 78 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1989 A novel 17 kD heparin-binding growth factor (HBGF-8) in bovine uterus: purification and N-terminal amino acid sequence. Biochemical and biophysical research communications 217 2610682
2018 Neural Stem Cells Behave as a Functional Niche for the Maturation of Newborn Neurons through the Secretion of PTN. Neuron 86 30497772
2005 Increased keratinocyte proliferation by JUN-dependent expression of PTN and SDF-1 in fibroblasts. Journal of cell science 84 15840658
2014 Functional receptors and intracellular signal pathways of midkine (MK) and pleiotrophin (PTN). Biological & pharmaceutical bulletin 75 24694599
1990 Heparin-binding neurotrophic factor (HBNF) and MK, members of a new family of homologous, developmentally regulated proteins. Biochemical and biophysical research communications 67 1700712
2019 Downregulation of circular RNA circ-LDLRAD3 suppresses pancreatic cancer progression through miR-137-3p/PTN axis. Life sciences 61 31521692
2019 Connecting Metainflammation and Neuroinflammation Through the PTN-MK-RPTPβ/ζ Axis: Relevance in Therapeutic Development. Frontiers in pharmacology 59 31031625
1992 Expression of the HBNF (heparin-binding neurite-promoting factor) gene in the brain of fetal, neonatal and adult rat: an in situ hybridization study. Brain research. Developmental brain research 55 1477961
1991 HBNF and MK, members of a novel gene family of heparin-binding proteins with potential roles in embryogenesis and brain function. Progress in growth factor research 53 1773041
2010 Lung cancer cell migration is regulated via repressing growth factor PTN/RPTP β/ζ signaling by menin. Oncogene 51 20639902
2000 Influence of the human endogenous retrovirus-like element HERV-E.PTN on the expression of growth factor pleiotrophin: a critical role of a retroviral Sp1-binding site. Oncogene 42 10962555
2018 Chemotherapy-driven increases in the CDKN1A/PTN/PTPRZ1 axis promote chemoresistance by activating the NF-κB pathway in breast cancer cells. Cell communication and signaling : CCS 38 30497491
2005 Effects of pleiotrophin (PTN) over-expression on mouse long bone development, fracture healing and bone repair. Calcified tissue international 38 15812580
2020 Long noncoding RNA OIP5-AS1 mediates resistance to doxorubicin by regulating miR-137-3p/PTN axis in osteosarcoma. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 37 32460190
2019 The PTN-PTPRZ signal activates the AFAP1L2-dependent PI3K-AKT pathway for oligodendrocyte differentiation: Targeted inactivation of PTPRZ activity in mice. Glia 36 30667096
2002 Pleiotrophin (PTN) and midkine (MK) mRNA expression in eutopic and ectopic endometrium in advanced stage endometriosis. Molecular human reproduction 33 11912283
2020 Discovery of PTN as a serum-based biomarker of pro-metastatic prostate cancer. British journal of cancer 32 33288843
2005 Miple1 and miple2 encode a family of MK/PTN homologues in Drosophila melanogaster. Development genes and evolution 31 16220264
1991 Isolation from bovine brain and structural characterization of HBNF, a heparin-binding neurotrophic factor. Growth factors (Chur, Switzerland) 31 2049182
2019 miR-627-3p inhibits osteosarcoma cell proliferation and metastasis by targeting PTN. Aging 30 31413208
2020 Down-regulation of circ-PTN suppresses cell proliferation, invasion and glycolysis in glioma by regulating miR-432-5p/RAB10 axis. Neuroscience letters 29 32629066
2022 Luteolin attenuates the chemoresistance of osteosarcoma through inhibiting the PTN/β-catenin/MDR1 signaling axis by upregulating miR-384. Journal of bone oncology 27 35493691
2019 Genome-wide screening identifies oncofetal lncRNA Ptn-dt promoting the proliferation of hepatocellular carcinoma cells by regulating the Ptn receptor. Oncogene 23 30643194
2003 The angiogenic peptide pleiotrophin (PTN/HB-GAM) is expressed in fracture healing: an immunohistochemical study in rats. Archives of orthopaedic and trauma surgery 23 14586627
2021 circ_PTN contributes to -cisplatin resistance in glioblastoma via PI3K/AKT signaling through the miR-542-3p/PIK3R3 pathway. Molecular therapy. Nucleic acids 22 34853725
2015 Size-dependent electronic structure controls activity for ethanol electro-oxidation at Ptn/indium tin oxide (n = 1 to 14). Physical chemistry chemical physics : PCCP 22 26018430
2014 PTN signaling: Components and mechanistic insights in human ovarian cancer. Molecular carcinogenesis 22 25418856
1999 Glycosaminoglycans promote HARP/PTN dimerization. Biochemical and biophysical research communications 21 10600521
2020 CircRNA-PTN Sponges miR-326 to Promote Proliferation in Hepatocellular Carcinoma. OncoTargets and therapy 20 32581550
2013 Anaplastic lymphoma kinase: "Ligand Independent Activation" mediated by the PTN/RPTPβ/ζ signaling pathway. Biochimica et biophysica acta 19 23777859
2012 Pleiotrophin (PTN) expression and function and in the mouse mammary gland and mammary epithelial cells. PloS one 18 23077670
2009 Pleiotrophin (PTN) is expressed in vascularized human atherosclerotic plaques: IFN-{gamma}/JAK/STAT1 signaling is critical for the expression of PTN in macrophages. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 18 19917672
2018 Reactions of Cyclometalated Platinum(II) [Pt(N∧C)(PR3)Cl] Complexes with Imidazole and Imidazole-Containing Biomolecules: Fine-Tuning of Reactivity and Photophysical Properties via Ligand Design. Inorganic chemistry 16 30376305
2017 Ptn functions downstream of C/EBPβ to mediate the effects of cAMP on uterine stromal cell differentiation through targeting Hand2 in response to progesterone. Journal of cellular physiology 16 28657144
2017 miR-182 aids in receptive endometrium development in dairy goats by down-regulating PTN expression. PloS one 16 28678802
1993 Genomic organization of the human HBNF gene and characterization of an HBNF variant protein as a splice mutant. Biochemical and biophysical research communications 16 8484754
2012 Synthesis, characterization, and DNA-binding studies of ruthenium complexes [Ru(tpy)(ptn)]2+ and Ru(dmtpy)(ptn)]2+. Journal of inorganic biochemistry 15 22687492
2023 Single-cell RNA sequencing reveals the mediatory role of cancer-associated fibroblast PTN in hepatitis B virus cirrhosis-HCC progression. Gut pathogens 14 37259127
2021 RNA binding protein GNL3 up-regulates IL24 and PTN to promote the development of osteoarthritis. Life sciences 14 33358901
2021 The ERK/CREB/PTN/syndecan-3 pathway involves in heparin-mediated neuro-protection and neuro-regeneration against cerebral ischemia-reperfusion injury following cardiac arrest. International immunopharmacology 14 34153666
2013 Intranasal immunization with W 80 5EC adjuvanted recombinant RSV rF-ptn enhances clearance of respiratory syncytial virus in a mouse model. Human vaccines & immunotherapeutics 13 24326268
2014 Cocaine- and amphetamine-regulated transcript facilitates the neurite outgrowth in cortical neurons after oxygen and glucose deprivation through PTN-dependent pathway. Neuroscience 12 25010400
2022 LncRNA PITPNA-AS1/miR-223-3p/PTN axis regulates malignant progression and stemness in lung squamous cell carcinoma. Journal of clinical laboratory analysis 10 35588441
2020 PTN-PTPRZ signalling is involved in deer antler stem cell regulation during tissue regeneration. Journal of cellular physiology 9 33111346
2011 PAd-shRNA-PTN reduces pleiotrophin of pancreatic cancer cells and inhibits neurite outgrowth of DRG. World journal of gastroenterology 9 21677838
2023 The Combination of Quantitative Proteomics and Systems Genetics Analysis Reveals that PTN Is Associated with Sleep-Loss-Induced Cognitive Impairment. Journal of proteome research 8 37611228
2020 Up-regulation of miR-137 can inhibit PTN in target manner to regulate PTN/PTPRZ pathway to prevent cognitive dysfunction caused by propofol. American journal of translational research 8 33312384
2002 Pd(II)- and Pt(II)-cimetidine complexes. Crystal structure of trans-[Pt(N,S-cimetidine)(2)]Cl(2)(*)12H(2)O. Journal of inorganic biochemistry 8 12062128
2023 Implication of the PTN/RPTPβ/ζ Signaling Pathway in Acute Ethanol Neuroinflammation in Both Sexes: A Comparative Study with LPS. Biomedicines 7 37238989
2018 Hmgb3 Induces the Differentiation of Uterine Stromal Cells Through Targeting Ptn. Reproductive sciences (Thousand Oaks, Calif.) 7 30081728
1995 Chromosomal assignment of the heparin-binding cytokine genes MDK and PTN in mouse and man. Cytogenetics and cell genetics 7 7835084
1992 Anti-viral activity of human recombinant heparin-binding proteins HBNF and MK. Biochemical and biophysical research communications 7 1335242
2024 PTN from Leydig cells activates SDC2 and modulates human spermatogonial stem cell proliferation and survival via GFRA1. Biological research 6 39285301
2024 Astrocyte-derived PTN alleviates deficits in hippocampal neurogenesis and cognition in models of multiple sclerosis. Stem cell reports 6 39729991
2020 Long Non-Coding RNA AGAP2-AS1/miR-628-5p/PTN Axis Modulates Proliferation, Migration, Invasion, and Apoptosis of Glioma Cells. Cancer management and research 6 32801858
2025 PTN activity in quiescent neural stem cells mediates Shank3 overexpression-induced manic behavior. Nature communications 5 40069581
2025 PTN secreted by cardiac fibroblasts promotes myocardial fibrosis and inflammation of pressure overload-induced hypertrophic cardiomyopathy through the PTN-SDC4 pathway. Life sciences 4 39765325
2025 Tenacissoside G reverses paclitaxel resistance by inhibiting Src/PTN/P-gp signaling axis activation in ovarian cancer cells. Journal of natural medicines 3 40195205
2024 Mea6/cTAGE5 cooperates with TRAPPC12 to regulate PTN secretion and white matter development. iScience 3 38439956
2024 A novel risk classification model integrating CEA, ctDNA, and pTN stage for stage 3 colon cancer: a post hoc analysis of the IDEA-France trial. The oncologist 3 39011625
2024 Pt-N catalytic centres concisely enhance interfacial charge transfer in amines functionalized Pt@MOFs for selective conversion of CO2 to CH4. Journal of colloid and interface science 2 38850864
2024 Effects of pleiotrophin (PTN) on the FAK inhibitor Y15 in breast cancer cells. International journal of biological macromolecules 2 39322128
2019 Evaluation of Serum Biomarkers (FGF-2, HGF, MIF and PTN) in Patients With Testicular Germ Cell Cancer. In vivo (Athens, Greece) 2 31662522
2007 [Construction of the recombinant adenovirus mediated shRNA to silence PTN in pancreatic carcinoma and the effect of DRGn on neurite in vitro]. Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 2 17825221
1992 [Clinical pathology of hypopharyngeal cancer--comparison between TN and pTN]. Nihon Jibiinkoka Gakkai kaiho 2 1569513
2025 The lncrna HMMR-AS1 promotes the malignant progression of ovarian cancer cells by regulating the miR-627-3p/PTN axis. Journal of ovarian research 1 40462168
2025 Targeting the HNRNPA2B1/HDGF/PTN Axis to Overcome Radioresistance in Non-Small Cell Lung Cancer. Antioxidants & redox signaling 1 40643435
2024 scRNA-Seq Analysis Revealed CAFs Regulating HCC Cells via PTN Signaling. Journal of hepatocellular carcinoma 1 39582814
2023 Pt-N Coordination Rendering the Chemotherapeutic Agent with Photoactivated ROS Generation and Self-Reporting Cell Uptake. ACS applied bio materials 1 36949576
2020 Positive association between PTN polymorphisms and schizophrenia in Northeast Chinese Han population. Psychiatric genetics 1 32868733
2016 Investigating the mechanism of the selective hydrogenation reaction of cinnamaldehyde catalyzed by Ptn clusters. Journal of molecular modeling 1 27444877
2026 Added value of tumor-stroma ratio to postsurgery circulating tumor DNA and pTN stage in risk stratification of patients with stage III colon cancer treated with adjuvant chemotherapy. ESMO open 0 41483629
2026 Deciphering Key Descriptors for Scaling Relationships in Graphene-Supported Ptn Clusters via Machine Learning. Small (Weinheim an der Bergstrasse, Germany) 0 41615214
2026 Cardiac PTN-SIRT1 axis alleviates oxidative stress and promotes mitochondrial energy reprogramming to mitigate doxorubicin-induced cardiotoxicity through AMPK/PGC1α signaling. Acta biochimica et biophysica Sinica 0 41640280
2026 ICAM2 loss drives 5-fluorouracil resistance via TGF-β/Smad/SP1/PTN-dependent apoptosis evasion and macrophage remodeling in gastric cancer. World journal of gastroenterology 0 41693979
2026 PTN/IGF-2 signaling modulates endometrial decidualization and immune cell trafficking to facilitate pregnancy maintenance. Frontiers in immunology 0 41948339
2025 Targeting the PTN/PTPRZ1-ROS Pathway to Promote Bone Regeneration. Biomedicines 0 40149671
2020 Long Non-Coding RNA AGAP2-AS1/miR-628-5p/PTN Axis Modulates Proliferation, Migration, Invasion, and Apoptosis of Glioma Cells [Retraction]. Cancer management and research 0 33116829