Affinage

PDGFC

Platelet-derived growth factor C · UniProt Q9NRA1

Length
345 aa
Mass
39.0 kDa
Annotated
2026-06-10
72 papers in source corpus 30 papers cited in narrative 31 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

PDGF-C is a secreted, protease-activated growth factor that signals through PDGFRα to drive proliferation, survival, migration, and matrix remodeling in mesenchymal, endothelial, and myeloid cell populations (PMID:10806482, PMID:11297552). It is synthesized as a latent multidomain dimer in which an N-terminal CUB domain restrains a C-terminal cystine-knot growth factor domain (GFD); cleavage at a defined site between the two domains liberates the GFD, which binds PDGFRα homodimers and PDGFRα/β heterodimers but not PDGFRβ homodimers (PMID:10806482, PMID:11297552, PMID:12598536). This activating cleavage is carried out by plasmin in vivo and by tPA, matriptase, and uPA in cellular contexts, with processing being rate-limiting for activity (PMID:22035541, PMID:18172073, PMID:17460299), and full-length PDGF-C additionally requires N-glycosylation at Asn254 to gain receptor-activating capacity (PMID:34109212). Downstream of PDGFRα, PDGF-C engages Akt/Bad signaling to suppress apoptosis and drives chemokine and matrix programs, including CCL2/CCL5 induction in fibroblasts and MMP-2/MMP-9 induction with monocyte chemotaxis (PMID:24421315, PMID:18184860, PMID:18573494). Genetic epistasis in mice establishes that PDGF-C and PDGF-A together account for all PDGFRα-dependent development of craniofacial structures, the neural tube, and mesodermal organs, with Pdgfc-/- animals dying perinatally from complete secondary palate cleft (PMID:15361870); a promoter SNP that reduces PDGF-C transcription is functionally linked to human cleft lip/palate susceptibility (PMID:19092777). PDGF-C is an active node in fibrosis and cancer, acting as a macrophage-derived pro-fibrotic and pro-inflammatory amplifier in kidney injury and as an autocrine/paracrine driver of tumor growth, invasion, metastasis, and therapy resistance across Ewing tumors, breast, pancreatic, prostate, and GIST models (PMID:18184860, PMID:12032822, PMID:33603171, PMID:36384875, PMID:40993441). Its abundance is tuned at multiple levels: transcriptionally by Egr-1 downstream of angiotensin II/AT1R, by EWS/FLI-1, by STAT4, and by H3K27 acetylation (PMID:18272536, PMID:11313995, PMID:40993441, PMID:36384875); post-transcriptionally by HuR-mediated mRNA stabilization via 3'-UTR AU-rich elements and by FTO/m6A/YTHDF2 control of transcript stability (PMID:25383675, PMID:35422475); and post-translationally by SUMO-1 modification at Lys314, which redirects a portion of the protein to the nucleus (PMID:16443219). Its activity is further modulated by the extracellular partner FREM1, which binds PDGF-C and shapes the duration and amplitude of PDGFRα signaling (PMID:24046351), and by N-terminally truncated splice variants that heterodimerize with full-length PDGF-C to alter its secretion and activity (PMID:18588873, PMID:31542979).

Mechanistic history

Synthesis pass · year-by-year structured walk · 30 steps
  1. 2000 High

    Established the defining feature of PDGF-C: unlike classical PDGFs it is a latent ligand that must be proteolytically processed to release an active growth factor domain that activates PDGFRα.

    Evidence Receptor binding assays, transgenic overexpression, and genetic analysis of Pdgfra-/- kidneys

    PMID:10806482

    Open questions at the time
    • Identity of the physiological protease(s) not defined
    • Receptor selectivity among PDGFRα/β configurations not yet resolved
  2. 2001 High

    Defined the CUB–GFD two-domain architecture and the receptor specificity, showing the GFD binds PDGFRα homodimers and PDGFRα/β heterodimers but not PDGFRβ homodimers, with a serum-sensitive interdomain cleavage event releasing the GFD.

    Evidence Competition binding, immunoprecipitation on dual-receptor cells, recombinant protein characterization, and diabetic wound-healing model

    PMID:11297552

    Open questions at the time
    • Specific protease not identified
    • Quantitative receptor affinities for each dimer configuration not established
  3. 2001 Medium

    Mapped PDGF-C genomic structure and tissue expression, localizing the cleavage site to exon 4 and identifying smooth muscle cells as a major source with mitogenic action on coronary artery SMCs.

    Evidence FISH mapping, genomic sequencing, and SMC stimulation assays

    PMID:11342471

    Open questions at the time
    • Single-lab functional data
    • In vivo relevance of SMC-derived PDGF-C not tested
  4. 2003 Medium

    Resolved the biophysical class of the GFD, showing a cystine-knot fold with three intramonomeric disulfides and greater structural similarity to VEGF than PDGF-B.

    Evidence Ellman assay, CD/NMR/IR spectroscopy on recombinant protein, and homology modeling

    PMID:12598536

    Open questions at the time
    • No experimental high-resolution structure
    • Homology model is computational
  5. 2004 High

    Defined the in vivo developmental function through genetic epistasis, showing PDGF-C and PDGF-A together account for all PDGFRα-dependent craniofacial, neural tube, and mesodermal development, with Pdgfc loss causing fatal palatal clefting.

    Evidence Single and double knockout mice with embryo phenotyping

    PMID:15361870

    Open questions at the time
    • Cell-type-specific contributions not dissected
    • Mechanism of redundancy with PDGF-A not resolved
  6. 2008 High

    Identified the dominant physiological activating protease, showing plasmin processes latent PDGF-C in vivo (vitreous), whereas tPA dominates only in cultured cells.

    Evidence In vitro processing assays with inhibitor blocking using patient and animal vitreous specimens

    PMID:17460299 PMID:18172073

    Open questions at the time
    • Tissue-to-tissue variation in protease usage not mapped
    • Regulation of processing rate not defined
  7. 2012 High

    Defined the cellular protease repertoire and processing intermediates, identifying tPA and matriptase as major cleavers (with uPA contributing) acting in two steps to generate the active GFD dimer.

    Evidence Reconstituted in vitro proteolysis, cleavage-site mutagenesis, protease inhibitors, and cell migration/proliferation assays in breast cancer

    PMID:22035541

    Open questions at the time
    • Relative contribution of each protease in vivo not quantified
    • Regulation of the hemidimer-to-GFD-dimer transition unknown
  8. 2021 Medium

    Established N-glycosylation at Asn254 as required for activation of full-length PDGF-C, distinguishing it from glycosylation sites dispensable for activity.

    Evidence Site-directed mutagenesis with secretion/trafficking controls and PDGFRα signaling assays

    PMID:34109212

    Open questions at the time
    • Mechanism by which Asn254 glycan enables activation not defined
    • Single-lab finding
  9. 2014 Medium

    Linked PDGF-C/PDGFRα to a pro-survival signaling output, showing Akt/Bad phosphorylation that suppresses caspase activation and PARP cleavage in macrophages.

    Evidence Recombinant ligand stimulation, phospho-Western blots, caspase assays, and PDGF-C knockdown xenografts

    PMID:24421315

    Open questions at the time
    • Direct receptor-to-Akt coupling not isolated from other inputs
    • Single-lab finding
  10. 2013 Medium

    Identified FREM1 as a direct extracellular binding partner that positively tunes the amplitude and duration of PDGFRα signaling and downstream matrix output.

    Evidence Binding/co-IP, fibroblast stimulation from Frem1-mutant mice, Timp1 and collagen deposition readouts

    PMID:24046351

    Open questions at the time
    • Stoichiometry and structural basis of FREM1–PDGF-C binding unknown
    • Single-lab finding
  11. 2008 High

    Established transcriptional control of PDGF-C by the angiotensin II/AT1R–Egr-1 axis at a defined upstream promoter element, operating selectively in neonatal but not adult smooth muscle cells.

    Evidence Reporter assays, EMSA, ChIP, and DNAzyme inhibition of Egr-1 with qRT-PCR

    PMID:18272536

    Open questions at the time
    • Basis of the neonatal-versus-adult difference not resolved
    • Other inputs converging on the promoter not mapped
  12. 2008 Medium

    Connected reduced PDGF-C transcription to human disease, showing a promoter SNP that abolishes regulatory motifs and reduces promoter activity is associated with cleft lip/palate susceptibility.

    Evidence Promoter reporter transfection, sequence analysis, and SNP genotyping

    PMID:19092777

    Open questions at the time
    • Causality in patient tissue not demonstrated
    • Effect on protein levels in vivo not measured
  13. 2006 Medium

    Revealed a post-translational fate beyond secretion, showing SUMO-1 modification at Lys314 produces a nuclear, partly chromatin-associated form that is reduced in papillary thyroid carcinoma.

    Evidence Subcellular fractionation, SUMO-1 co-IP, and immunohistochemistry

    PMID:16443219

    Open questions at the time
    • Function of the nuclear form unknown
    • SUMO ligase and signals controlling modification not identified
  14. 2014 Medium

    Established post-transcriptional stabilization of PDGF-C, showing HuR binds two 3'-UTR AU-rich elements to upregulate PDGF-C mRNA under stress in breast cancer cells.

    Evidence RNA immunoprecipitation, 3'-UTR reporter, HuR perturbation, and mRNA stability assays

    PMID:25383675

    Open questions at the time
    • Stress signals driving HuR engagement not defined
    • Single-lab finding
  15. 2022 Medium

    Added m6A-based regulation of PDGFC, showing FTO removes 3'-UTR m6A marks to stabilize the transcript, while m6A accumulation triggers YTHDF2-dependent decay, with the FTO–PDGFC axis reactivating Akt to promote pancreatic cancer growth.

    Evidence m6A-seq, MeRIP-qPCR, RIP, luciferase reporter, and FTO perturbation in vitro and in vivo

    PMID:35422475

    Open questions at the time
    • Specific m6A sites controlling decay not pinpointed
    • Single-lab finding
  16. 2025 Medium

    Extended transcriptional regulation to a therapy-resistance context, identifying STAT4 as a direct activator of PDGFC that drives autocrine PDGFR-Rap1-MAPK signaling and enzalutamide resistance in prostate cancer.

    Evidence Luciferase reporter, ChIP, PDGFC silencing, in vitro proliferation assays, and xenografts

    PMID:40993441

    Open questions at the time
    • Generality of the Rap1-MAPK output across cell types not tested
    • Single-lab finding
  17. 2008 Medium

    Implicated PDGF-C as a myeloid effector in vascular inflammation, showing it induces MMP-9 expression, enhances MMP-2/MMP-9 secretion, and attracts monocytes.

    Evidence qPCR, ELISA/zymography, and Boyden chamber migration assays

    PMID:18573494

    Open questions at the time
    • Receptor dependence of MMP induction not confirmed
    • In vivo relevance not tested in this study
  18. 2008 High

    Defined a pathogenic role in renal fibrosis, showing macrophage-derived PDGF-C is a fibroblast mitogen and chemokine inducer that drives a pro-inflammatory amplification loop, with neutralization or knockout reducing fibrosis.

    Evidence Anti-PDGF-C neutralization and Pdgfc-/- mice in the UUO model plus in vitro fibroblast assays

    PMID:18184860

    Open questions at the time
    • Upstream trigger of macrophage PDGF-C production not defined
    • Contribution of PDGFRα versus β to the loop not separated here
  19. 2010 Medium

    Revealed an indirect pro-angiogenic action in glomerular disease, showing PDGF-C infusion increases endothelial proliferation and strongly upregulates FGF-2 in glomerular endothelial cells.

    Evidence PDGF-C infusion/antagonism in rat nephritis and microangiopathy models with in vitro glomerular endothelial assays

    PMID:20489153

    Open questions at the time
    • Direct versus paracrine endothelial effects not fully separated
    • Single-lab finding
  20. 2012 High

    Demonstrated organ specificity of PDGF-C in fibrosis, showing it protects against kidney fibrosis via PDGFRα/β signaling but not against liver fibrosis, where PDGF-B/D–PDGFRβ predominate.

    Evidence Pdgfc-/- mice and neutralizing antibody across UUO and bile duct ligation models with receptor signaling Westerns

    PMID:23141925

    Open questions at the time
    • Molecular basis of organ specificity not defined
    • Cross-talk among PDGF isoforms not dissected
  21. 2001 Medium

    Linked PDGF-C to oncogenic transcription, showing the EWS/FLI-1 fusion transcriptionally upregulates PDGF-C in Ewing family tumors in an EWS/ETS-specific manner.

    Evidence Retroviral cDNA screen and EWS/FLI modulation in EFT cell lines

    PMID:11313995

    Open questions at the time
    • Direct versus indirect EWS/FLI regulation of the promoter not established
    • Single-lab finding
  22. 2002 Medium

    Demonstrated functional dependence of tumor phenotype on autocrine PDGF-C, showing a dominant-negative PDGF-C and PDGFR inhibition block anchorage-independent growth.

    Evidence Dominant-negative mutagenesis, soft-agar assays, and AG1296 inhibition in EFT and fibroblast models

    PMID:12032822

    Open questions at the time
    • In vivo tumor dependence not tested here
    • Single-lab finding
  23. 2012 Medium

    Established a paracrine pro-metastatic role, showing tumor-derived PDGF-C rescues hepatic stellate cells via PAK-2 and that PDGF-C knockdown inhibits liver metastasis.

    Evidence PDGF-C knockdown in colon carcinoma, recombinant ligand on HSC, PAK-2 siRNA, and nude mouse metastasis model

    PMID:22362252

    Open questions at the time
    • Receptor mediating the HSC response not identified
    • Single-lab finding
  24. 2021 Medium

    Extended paracrine tumor signaling to the stroma, showing CAF-derived PDGFC activates PDGFRA-SLUG signaling to drive GIST growth and metastasis.

    Evidence CAF isolation, co-culture, PDGFC perturbation, and in vivo metastasis model

    PMID:33603171

    Open questions at the time
    • Direct PDGFRA-to-SLUG mechanism not fully mapped
    • Single-lab finding
  25. 2022 Medium

    Linked epigenetic activation of PDGFC to drug resistance, showing H3K27 acetylation activates PDGFC, which drives gemcitabine resistance via PDGFR-PI3K-AKT, reversible by imatinib.

    Evidence H3K27ac ChIP, PDGFC silencing, signaling Westerns, and patient-derived xenografts

    PMID:36384875

    Open questions at the time
    • Writer/eraser controlling the H3K27ac mark not identified
    • Single-lab finding
  26. 2019 Medium

    Characterized regulatory splice variants, showing a truncated PDGF-C lacking signal peptide and CUB domain forms intracellular dimers and heterodimerizes with full-length protein to enhance transformation and invasion.

    Evidence Expression constructs, localization imaging, soft-agar and Matrigel assays, and PDGF-C knockdown

    PMID:31542979

    Open questions at the time
    • Endogenous expression and physiological relevance of the variant unclear
    • Single-lab finding
  27. 2008 Medium

    Described a dominant-negative splice isoform, showing a non-secreted N-terminally truncated PDGF-Cb heterodimerizes with full-length protein, retaining and degrading it.

    Evidence Expression constructs, localization, and co-IP for heterodimers

    PMID:18588873

    Open questions at the time
    • In vivo occurrence and functional impact not established
    • Single-lab finding
  28. 2023 Low

    Proposed a mitogenic mechanism via ribosome biogenesis control, with PDGF-C downregulating BOP1 to promote proliferation.

    Evidence Conditioned medium treatment, BOP1 perturbation, and Pdgfc-/- tissues in HEK293A assays

    PMID:37615370

    Open questions at the time
    • Indirect conditioned-medium exposure limits mechanistic attribution
    • Receptor dependence of BOP1 regulation not shown
  29. 2023 Medium

    Implicated PDGF-C in endothelial mitochondrial homeostasis, showing it increases OPA1 and reduces DRP1 Ser616 phosphorylation to restore mitochondrial networks under high glucose.

    Evidence Recombinant PDGF-C on aortic endothelial cells with Western blot, morphology imaging, and Seahorse flux

    PMID:36901825

    Open questions at the time
    • Signaling link from PDGFRα to mitochondrial dynamics machinery not defined
    • Single-lab finding
  30. 2025 Low

    Suggested a niche-maintenance role, with PDGFC supporting isolation and quiescent maintenance of neural stem cells permissive for oligodendrocyte progenitor transition.

    Evidence NSC culture in PDGFC medium with comparative expression and lineage assays (preprint)

    Open questions at the time
    • Preprint, not peer-reviewed
    • Descriptive culture assay without receptor-level mechanism

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple regulatory layers—proteolytic activation, glycosylation, SUMOylation, m6A/HuR mRNA control, and splice-variant dimerization—are integrated to set PDGF-C activity in a given tissue, and the structural basis of its receptor and FREM1 interactions, remains unresolved.
  • No experimental high-resolution structure of the GFD–receptor complex
  • No integrated model coupling activation, modification, and transcriptional control
  • Tissue-specific protease and receptor usage not systematically mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 3 GO:0060089 molecular transducer activity 2 GO:0098772 molecular function regulator activity 1
Localization
GO:0005576 extracellular region 3 GO:0005829 cytosol 2 GO:0005634 nucleus 1
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 3 R-HSA-392499 Metabolism of proteins 2 R-HSA-1266738 Developmental Biology 1
Partners
FREM1PDGFRAPDGFRBPLATPLGST14

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 PDGF-C is a protease-activated ligand that binds to and activates the PDGF alpha-receptor (PDGFRα). Proteolytic cleavage is required to release the growth factor domain (GFD) from the CUB domain for receptor activation. Receptor binding assays, transgenic mouse overexpression, in situ hybridization, genetic analysis of Pdgfra-/- kidneys Nature cell biology High 10806482
2001 PDGF-C is a multidomain protein with an N-terminal CUB domain and a C-terminal growth factor domain (GFD). The GFD (PDGF-CC) binds with high affinity to PDGFRα homodimers and PDGFRα/β heterodimers, but not PDGFRβ homodimers. A serum-sensitive cleavage site between the CUB and GFD domains releases the active GFD. Competition binding assays, immunoprecipitation on cells bearing both receptor types, recombinant protein characterization, mitogenesis assays, diabetic mouse wound healing model The Journal of biological chemistry High 11297552
2001 PDGF-C genomic structure has 6 exons; the CUB domain is encoded by exons 2–3 and the proteolytic cleavage site activating the growth factor domain is located in exon 4. PDGF-C is expressed predominantly in smooth muscle cells and stimulates coronary artery smooth muscle cell proliferation. FISH chromosomal mapping, genomic DNA sequencing, cell stimulation assays Circulation Medium 11342471
2003 The GFD of PDGF-C contains 12 cysteine residues with three intramonomeric disulfide bonds consistent with cystine knot superfamily membership. Structural characterization by CD, fluorescence, NMR, and infrared spectroscopy indicates predominantly beta-sheet secondary structure; homology modeling shows greater structural similarity to VEGF than to PDGF-B. Ellman assay, CD spectroscopy, NMR spectroscopy, infrared spectroscopy, homology modeling The Journal of biological chemistry Medium 12598536
2004 Pdgfc-/- mice die perinatally due to complete secondary palate cleft. Pdgfc-/- Pdgfa-/- double knockouts phenocopy Pdgfra-/- (cleft face, subepidermal blistering, renal cortex mesenchyme deficiency, spina bifida, skeletal and vascular defects), establishing by genetic epistasis that PDGF-A and PDGF-C together account for all PDGFRα signaling in craniofacial, neural tube, and mesodermal development. Genetic knockout, double-knockout epistasis, embryo phenotyping Nature genetics High 15361870
2001 PDGF-C expression in Ewing family tumors (EFT) is transcriptionally upregulated by the chimeric EWS/FLI-1 transcription factor and this regulation is EWS/ETS-specific. PDGF-C expression depends on EWS/FLI activity in EFT cell lines. Retroviral cDNA biological screen, differential gene regulation, EWS/FLI knockdown/modulation in EFT cell lines Oncogene Medium 11313995
2002 A dominant-negative form of PDGF-C that is secreted and processed but has greatly reduced PDGFRα agonist activity inhibits anchorage-independent growth in EFT cell lines and in a PDGF-C-driven fibroblast transformation model, demonstrating that autocrine PDGF-C/PDGFRα signaling drives EFT malignant phenotype. Dominant-negative mutagenesis, soft-agar colony formation assay, PDGFR inhibitor AG1296 Oncogene Medium 12032822
2008 In renal fibrosis, PDGF-C is produced largely by infiltrating macrophages. PDGF-C acts as a potent mitogen for renal fibroblasts and induces chemokine expression (CCL2, CCL5). Neutralization of PDGF-C reduces renal fibrosis, interstitial myofibroblast accumulation, and leukocyte infiltration; Pdgfc-/- mice show reduced fibrosis and inflammation after ureteral obstruction, suggesting a pro-inflammatory amplification loop. Anti-PDGF-C neutralizing antiserum in UUO mouse model, Pdgfc-/- mice, in vitro fibroblast mitogenesis and chemokine assays Journal of the American Society of Nephrology High 18184860
2012 PDGF-C neutralization or deficiency protects against kidney fibrosis by reducing PDGFRα and PDGFRβ signaling but does NOT protect against bile duct ligation-induced liver fibrosis, where PDGF-B and PDGF-D signaling through PDGFRβ predominates. This demonstrates organ-specific differential roles of PDGF receptor isoforms. Pdgfc-/- mice, neutralizing antibody, bile duct ligation and UUO fibrosis models, Western blot for receptor signaling, in vitro portal myofibroblast assays The American journal of pathology High 23141925
2012 In breast cancer, tPA (tissue plasminogen activator) and matriptase are the major proteases responsible for cleaving PDGF-C at a specific site identified by site-directed mutagenesis to release the active GFD from the CUB domain. uPA can also process PDGF-C. Processing appears to occur in two steps: first generating a hemidimer, then a growth factor domain dimer (GFD-D). Active PDGF-C drives autocrine proliferation and paracrine fibroblast migration. In vitro processing assay with recombinant PDGF-C, site-directed mutagenesis of cleavage site, protease inhibitors, cell proliferation/invasion/migration assays The Biochemical journal High 22035541
2008 Plasmin is the major protease responsible for processing latent PDGF-C to its active form in the vitreous of PVR patients and rabbits. Blocking plasmin activity eliminates most PDGF-C processing activity in vitreous samples. tPA, identified as the main protease in cultured cells, is a minority contributor in vivo. In vitro PDGF-C processing assay with native/recombinant substrate, Western blot for active PDGF-C and PDGFRα phosphorylation, alpha2-plasmin inhibitor blocking, vitreous specimens from patients and animals Investigative ophthalmology & visual science High 18172073
2007 PDGF-C is the predominant PDGF isoform in experimental and clinical PVR vitreous. PDGF-C is secreted in a latent form (CUB domain intact) and requires proteolytic processing for activation; processing activity was present in conditioned medium and vitreous even though latent PDGF-C accumulated, suggesting processing is rate-limiting. Western blot, ELISA, in vitro PDGF-C processing assay, vitreous specimens from PVR rabbits and patients Investigative ophthalmology & visual science Medium 17460299
2006 PDGF-C is SUMOylated by SUMO-1 at Lys314, producing a ~55 kDa form that localizes to the nucleus and is partly chromatin-associated. The non-SUMOylated ~39 kDa form is found at the cell membrane and cytosol. The SUMOylated form is reduced in papillary thyroid carcinoma tissue compared to non-neoplastic thyroid and cultured cells. Western blot fractionation, co-immunoprecipitation with SUMO-1, immunohistochemistry, subcellular fractionation Experimental cell research Medium 16443219
2013 FREM1 physically binds to PDGF-C, and this interaction regulates the duration and amplitude of downstream PDGFRα signaling. Loss of FREM1 reduces PDGF-C-stimulated Timp1 expression in fibroblasts, leading to decreased basement membrane collagen I deposition. This places FREM1 as a positive extracellular regulator of PDGF-C activity. Co-immunoprecipitation/binding assay (FREM1–PDGF-C), fibroblast stimulation assays from Frem1-mutant mice, Timp1 mRNA measurement, collagen deposition assay Disease models & mechanisms Medium 24046351
2008 Angiotensin II induces PDGF-C transcription in neonatal smooth muscle cells via AT1 receptor-dependent Egr-1 activation at an upstream Egr-1-binding element (~500 bp upstream) in the PDGF-C promoter. A G+C-rich proximal element is not involved. This axis does not operate in adult SMCs where Egr-1 induction by AngII does not drive PDGF-C. Transient transfection reporter assays, EMSA with nuclear extracts and recombinant proteins, ChIP, DNAzyme targeting Egr-1, qRT-PCR Nucleic acids research High 18272536
2008 The PDGF-C promoter SNP rs28999109 (-986 C>T) abolishes six overlapping transcription regulatory motifs and reduces PDGF-C promoter transcriptional activity by up to 80% in reporter transfection assays, functionally linking reduced PDGF-C expression to cleft lip/palate susceptibility. Promoter reporter transfection assays, sequence analysis, SNP genotyping European journal of human genetics Medium 19092777
2014 PDGF-C activates PDGFRα, leading to Akt and Bad phosphorylation in macrophages, which suppresses apoptosis by inhibiting caspase-3, -7, -8, and -9 and PARP cleavage. Tumor-associated macrophage apoptosis increases when PDGF-C is knocked down in breast cancer cells in vivo. Recombinant PDGF-C stimulation, Western blot for phospho-PDGFRα/Akt/Bad, caspase activity assay, PARP cleavage, PDGF-C knockdown tumor xenograft, TAM apoptosis measurement The Journal of biological chemistry Medium 24421315
2021 PDGF-C is glycosylated at three sites (Asn25, Asn55, Asn254). Mutation at Asn254 (N254A) specifically prevents activation of full-length PDGF-C and its capacity to signal via PDGFRα, without affecting protein expression, secretion, or ER/Golgi trafficking. Mutations at Asn25 and Asn55 do not affect activation. Site-directed mutagenesis, Western blot for protein expression/secretion, PDGFRα signaling assays Frontiers in molecular biosciences Medium 34109212
2022 FTO (RNA m6A demethylase) stabilizes PDGFC mRNA by reducing m6A modifications in the 3' UTR; increased m6A methylation in the absence of FTO leads to YTHDF2-dependent degradation of PDGFC mRNA. PDGFC upregulation by FTO reactivates the Akt signaling pathway to promote pancreatic cancer cell growth. m6A sequencing (m6A-seq), MeRIP-qPCR, RNA immunoprecipitation (RIP), luciferase reporter assay, FTO knockdown/overexpression, cell proliferation in vitro and in vivo Oncogene Medium 35422475
2021 CAF-derived PDGFC activates PDGFC-PDGFRA signal transduction in GIST cells, which upregulates SLUG (an EMT transcription factor and PDGFRA downstream target), driving tumor growth and metastasis via paracrine signaling. CAF isolation from human tumors, co-culture, PDGFC knockdown/overexpression, in vivo metastasis model, SLUG expression correlation Oncogene Medium 33603171
2022 PDGFC transcription in gemcitabine-resistant pancreatic cancer is epigenetically activated by H3K27 acetylation. PDGFC promotes gemcitabine resistance by activating the PDGFR-PI3K-AKT signaling pathway; PDGFR inhibitor imatinib synergizes with gemcitabine by blocking this pathway. ChIP for H3K27ac, PDGFC silencing, Western blot for PDGFR-PI3K-AKT, patient-derived xenograft model Molecular therapy Medium 36384875
2023 PDGF-C modulates mitochondrial dynamics in endothelial cells under high-glucose conditions: it increases OPA1 fusion protein expression, reduces DRP1 phosphorylation at Ser616, and restores fragmented mitochondrial network, partially compensating for high-glucose-induced bioenergetic alterations. Recombinant PDGF-C treatment of human aortic endothelial cells, Western blot for OPA1/DRP1pSer616, mitochondrial morphology imaging, Seahorse metabolic flux analysis International journal of molecular sciences Medium 36901825
2008 PDGF-C and PDGF-D induce MMP-9 mRNA expression in monocytes in a concentration-dependent manner, enhance secretion of MMP-2 and MMP-9, and attract THP-1 monocytes in a Boyden chamber migration assay. qPCR for MMP mRNA, ELISA/zymography for MMP secretion, Boyden chamber migration assay Atherosclerosis Medium 18573494
2014 HuR stabilizes PDGF-C mRNA by binding to two AU-rich elements (AREs) in the 3'-UTR, providing post-transcriptional upregulation of PDGF-C under cellular stress conditions in breast cancer cells. RNA immunoprecipitation, 3'-UTR reporter assay, HuR knockdown/overexpression, mRNA stability assay International journal of molecular sciences Medium 25383675
2010 PDGF-C infusion in rats with mesangioproliferative glomerulonephritis reduces mesangiolysis and microaneurysm formation, increases glomerular endothelial cell area and proliferation, and specifically up-regulates glomerular FGF-2 expression 27-fold in glomerular endothelial cells. PDGF-C also exerts indirect pro-angiogenic effects by inducing endothelial mitogens in mesangial cells and macrophages. PDGF-C infusion in rat nephritis model, PDGF-C antagonism, thrombotic microangiopathy mouse model, in vitro glomerular endothelial cell assays, FGF-2 mRNA quantification The American journal of pathology Medium 20489153
2012 Tumor cell-derived PDGF-C acts in a paracrine manner on hepatic stellate cells (HSC) to rescue them from growth inhibition; this effect is dependent on PAK-2 in HSC, as PAK-2 silencing in HSC blunts PDGF-C-mediated rescue. In vivo, PDGF-C knockdown in colon carcinoma cells prominently inhibits liver metastasis. PDGF-C knockdown in LS174T cells, recombinant PDGF-C treatment of HSC, PAK-2 siRNA in HSC, nude mouse liver metastasis model, whole genome array analysis Clinical & experimental metastasis Medium 22362252
2025 PDGFC facilitates enzalutamide resistance in prostate cancer by activating the PDGFR-Rap1-MAPK signaling pathway in an autocrine manner. STAT4 transcriptionally upregulates PDGFC by binding to a specific DNA sequence in the PDGFC promoter, demonstrated by luciferase and ChIP assays. qRT-PCR, Western blot, luciferase reporter assay, ChIP assay, PDGFC silencing, in vitro CCK8/colony/EdU assays, xenograft tumor model Journal of cancer research and clinical oncology Medium 40993441
2019 A truncated PDGF-C splice variant (t-PDGF-C) lacking the signal peptide and CUB domain forms intracellular homodimers that are retained intracellularly, but can be secreted as a heterodimer with full-length PDGF-C; ectopic expression of t-PDGF-C in cells expressing endogenous full-length PDGF-C enhances transformation and invasion. Expression constructs, Western blot, immunofluorescence localization, soft-agar anchorage-independent growth, Matrigel invasion assay, PDGF-C siRNA knockdown Growth factors (Chur, Switzerland) Medium 31542979
2008 A PDGF-C splice variant (PDGF-Cb) encoding an N-terminally truncated protein lacking signal peptide and CUB domain is produced as a cytoplasmic protein that is not secreted, but can form heterodimers with full-length PDGF-C, retaining it intracellularly and leading to its degradation, suggesting a dominant-negative regulatory mechanism. Expression constructs, Western blot, immunofluorescence localization, co-immunoprecipitation for heterodimer detection Experimental cell research Medium 18588873
2023 PDGF-C promotes cell proliferation partly by downregulating BOP1 (block of proliferation 1, a ribosome biogenesis regulator) at both mRNA and protein levels. BOP1 overexpression inhibits proliferation, and BOP1 knockdown promotes it; attenuation of BOP1 by PDGF-C is part of the mitogenic mechanism. Conditioned medium treatment, Western blot, qPCR, BOP1 overexpression/knockdown, Pdgfc-/- mouse tissues, HEK293A proliferation assays Cell biology international Low 37615370
2025 PDGFC supports isolation and maintenance of murine neural stem cells (NSCs) from the subventricular zone in quiescent and slowly proliferating states; NSCs in PDGFC have a quiescence gene profile more similar to SVZ tissue than EGF/FGF-grown NSCs. PDGFC-maintained NSCs can transition to oligodendrocyte progenitor cells (OPCs) when FGF is added. NSC isolation and culture in PDGFC-supplemented medium, comparative gene expression analysis, lineage differentiation assays bioRxivpreprint Low

Source papers

Stage 0 corpus · 72 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 PDGF-C is a new protease-activated ligand for the PDGF alpha-receptor. Nature cell biology 491 10806482
2002 Platelet-derived growth factor (PDGF) autocrine signaling regulates survival and mitogenic pathways in glioblastoma cells: evidence that the novel PDGF-C and PDGF-D ligands may play a role in the development of brain tumors. Cancer research 348 12097282
2001 Platelet-derived growth factor C (PDGF-C), a novel growth factor that binds to PDGF alpha and beta receptor. The Journal of biological chemistry 228 11297552
2004 A specific requirement for PDGF-C in palate formation and PDGFR-alpha signaling. Nature genetics 184 15361870
2005 Structural and functional specificities of PDGF-C and PDGF-D, the novel members of the platelet-derived growth factors family. The FEBS journal 169 16279938
2003 Novel PDGF family members: PDGF-C and PDGF-D. Cytokine & growth factor reviews 143 12651221
2008 PDGF-C is a proinflammatory cytokine that mediates renal interstitial fibrosis. Journal of the American Society of Nephrology : JASN 104 18184860
2001 Chromosomal location, exon structure, and vascular expression patterns of the human PDGFC and PDGFD genes. Circulation 104 11342471
2009 PDGF-C induces maturation of blood vessels in a model of glioblastoma and attenuates the response to anti-VEGF treatment. PloS one 98 19352490
2001 PDGF-C is an EWS/FLI induced transforming growth factor in Ewing family tumors. Oncogene 95 11313995
2000 The mouse Pdgfc gene: dynamic expression in embryonic tissues during organogenesis. Mechanisms of development 90 10960785
2018 PDGF-C and PDGF-D signaling in vascular diseases and animal models. Molecular aspects of medicine 87 29410092
2011 Extracellular matrix dynamics in hepatocarcinogenesis: a comparative proteomics study of PDGFC transgenic and Pten null mouse models. PLoS genetics 76 21731504
2014 Angiogenesis and expression of PDGF-C, VEGF, CD105 and HIF-1α in human glioblastoma. Neuropathology : official journal of the Japanese Society of Neuropathology 75 24612214
2008 Effects of PDGF-C and PDGF-D on monocyte migration and MMP-2 and MMP-9 expression. Atherosclerosis 70 18573494
2023 Age-associated microenvironmental changes highlight the role of PDGF-C in ER+ breast cancer metastatic relapse. Nature cancer 67 36914817
2003 Modulation of PDGF-C and PDGF-D expression during bleomycin-induced lung fibrosis. American journal of physiology. Lung cellular and molecular physiology 62 12972405
2003 PDGF-C expression in the developing and normal adult human kidney and in glomerular diseases. Journal of the American Society of Nephrology : JASN 60 12707385
2007 A potential role for PDGF-C in experimental and clinical proliferative vitreoretinopathy. Investigative ophthalmology & visual science 59 17460299
2002 Expression of a novel PDGF isoform, PDGF-C, in normal and diseased rat kidney. Journal of the American Society of Nephrology : JASN 59 11912250
2002 Expression analysis of PDGF-C in adult and developing mouse tissues. Mechanisms of development 57 11744381
2021 Cancer-associated fibroblast secretion of PDGFC promotes gastrointestinal stromal tumor growth and metastasis. Oncogene 52 33603171
2012 Platelet-derived growth factor (PDGF)-C neutralization reveals differential roles of PDGF receptors in liver and kidney fibrosis. The American journal of pathology 52 23141925
2022 RNA N6-methyladenosine demethylase FTO promotes pancreatic cancer progression by inducing the autocrine activity of PDGFC in an m6A-YTHDF2-dependent manner. Oncogene 50 35422475
2007 PDGF-C and -D induced proliferation/migration of human RPE is abolished by inflammatory cytokines. Investigative ophthalmology & visual science 48 18055825
2009 PDGF-C and -D and their receptors PDGFR-alpha and PDGFR-beta in atherosclerotic human arteries. European journal of clinical investigation 44 19292888
2008 The PDGF-C regulatory region SNP rs28999109 decreases promoter transcriptional activity and is associated with CL/P. European journal of human genetics : EJHG 44 19092777
2002 Dominant negative PDGF-C inhibits growth of Ewing family tumor cell lines. Oncogene 44 12032822
2014 Platelet-derived growth factor-C (PDGF-C) induces anti-apoptotic effects on macrophages through Akt and Bad phosphorylation. The Journal of biological chemistry 40 24421315
2012 Platelet-derived growth factor-C (PDGF-C) activation by serine proteases: implications for breast cancer progression. The Biochemical journal 40 22035541
2013 PDGF-C: a new performer in the neurovascular interplay. Trends in molecular medicine 36 23714575
2010 PDGF-C mediates glomerular capillary repair. The American journal of pathology 35 20489153
2003 Platelet-derived growth factor (PDGF)-C, a PDGF family member with a vascular endothelial growth factor-like structure. The Journal of biological chemistry 32 12598536
2021 Poricoic acid A suppresses TGF-β1-induced renal fibrosis and proliferation via the PDGF-C, Smad3 and MAPK pathways. Experimental and therapeutic medicine 26 33717232
2008 Plasmin is the major protease responsible for processing PDGF-C in the vitreous of patients with proliferative vitreoretinopathy. Investigative ophthalmology & visual science 24 18172073
2022 Imatinib facilitates gemcitabine sensitivity by targeting epigenetically activated PDGFC signaling in pancreatic cancer. Molecular therapy : the journal of the American Society of Gene Therapy 23 36384875
2000 A novel gene derived from developing spinal cords, SCDGF, is a unique member of the PDGF/VEGF family. FEBS letters 23 10858496
2012 Paracrine signalling in colorectal liver metastases involving tumor cell-derived PDGF-C and hepatic stellate cell-derived PAK-2. Clinical & experimental metastasis 22 22362252
2006 Over-expression of PDGF-C using a lung specific promoter results in abnormal lung development. Transgenic research 22 16830225
2008 Angiotensin II induction of PDGF-C expression is mediated by AT1 receptor-dependent Egr-1 transactivation. Nucleic acids research 21 18272536
2002 The expression of SCDGF/PDGF-C/fallotein and SCDGF-B/PDGF-D in the rat central nervous system. Mechanisms of development 21 11850188
2005 Elevated expression of PDGF-C in coxsackievirus B3-induced chronic myocarditis. European heart journal 20 15757958
2000 Identification of a novel platelet-derived growth factor-like gene, fallotein, in the human reproductive tract. Biochimica et biophysica acta 19 11004490
2023 Impact of Acute High Glucose on Mitochondrial Function in a Model of Endothelial Cells: Role of PDGF-C. International journal of molecular sciences 17 36901825
2006 PDGF-C controls proliferation and is down-regulated by retinoic acid in mouse embryonic palatal mesenchymal cells. Birth defects research. Part B, Developmental and reproductive toxicology 17 17066417
2002 Characterization of platelet-derived growth factor-C (PDGF-C): expression in normal and tumor cells, biological activity and chromosomal localization. The international journal of biochemistry & cell biology 17 11854040
2009 Expression of a novel PDGF isoform, PDGF-C, in experimental periapical lesions. Journal of endodontics 16 19249599
2009 Inverse correlation between PDGFC expression and lymphocyte infiltration in human papillary thyroid carcinomas. BMC cancer 16 19968886
2014 Post-transcriptional up-regulation of PDGF-C by HuR in advanced and stressed breast cancer. International journal of molecular sciences 15 25383675
2013 Regulation of PDGFC signalling and extracellular matrix composition by FREM1 in mice. Disease models & mechanisms 15 24046351
2007 Generation of conditional knockout alleles for PDGF-C. Genesis (New York, N.Y. : 2000) 15 17941048
2022 Visfatin-Induced Inhibition of miR-1264 Facilitates PDGF-C Synthesis in Chondrosarcoma Cells and Enhances Endothelial Progenitor Cell Angiogenesis. Cells 14 36359873
2014 Platelet-derived growth factor (PDGF)-C inhibits neuroretinal apoptosis in a murine model of focal retinal degeneration. Laboratory investigation; a journal of technical methods and pathology 14 24709779
2001 Molecular cloning of SCDGF-B, a novel growth factor homologous to SCDGF/PDGF-C/fallotein. Biochemical and biophysical research communications 14 11162582
2021 Expression and function of PDGF-C in development and stem cells. Open biology 13 34847773
2019 An oncogenic activity of PDGF-C and its splice variant in human breast cancer. Growth factors (Chur, Switzerland) 12 31542979
2006 Nuclear localisation of endogenous SUMO-1-modified PDGF-C in human thyroid tissue and cell lines. Experimental cell research 11 16443219
2018 PHD3 Acts as Tumor Suppressor in Mouse Osteosarcoma and Influences Tumor Vascularization via PDGF-C Signaling. Cancers 10 30563292
2008 The molecular cloning of platelet-derived growth factor-C (PDGF-C) gene of Gekko japonicus and its expression change in the spinal cord after tail amputation. Cellular and molecular neurobiology 8 18925432
2006 PDGF-C participates in branchial arch morphogenesis and is down-regulated by retinoic acid. Toxicology letters 8 16956736
2013 Bilaterally cleft lip and bilateral thumb polydactyly with triphalangeal component in a patient with two de novo deletions of HSA 4q32 and 4q34 involving PDGFC, GRIA2, and FBXO8 genes. American journal of medical genetics. Part A 7 24038848
2018 A Pdgf-cCreERT2 knock-in mouse model for tracing PDGF-C cell lineages during development. Genesis (New York, N.Y. : 2000) 4 29345101
2021 Glycosylation at Asn254 Is Required for the Activation of the PDGF-C Protein. Frontiers in molecular biosciences 3 34109212
2008 Identification and expression analysis of an N-terminally truncated isoform of human PDGF-C. Experimental cell research 3 18588873
2023 PDGF-C promotes cell proliferation partially via downregulating BOP1. Cell biology international 2 37615370
2025 PDGFC secreted by cancer-associated fibroblasts promotes epithelial-mesenchymal transition and immunosuppression in lung adenocarcinoma. Acta biochimica et biophysica Sinica 1 40501228
2016 [Effect of PDGF-C on biological characters of human dermal papilla cells in vitro]. Zhonghua zheng xing wai ke za zhi = Zhonghua zhengxing waike zazhi = Chinese journal of plastic surgery 1 30044068
2026 An Inhibitory Aptamer Against PDGF-C Overcomes Anti-VEGF Refractoriness and Reduces Choroidal Neovascularization and Fibrosis. Investigative ophthalmology & visual science 0 42138517
2025 PDGFC facilitates enzalutamide resistance in prostate cancer through activation of the Rap1-MAPK pathway. Journal of cancer research and clinical oncology 0 40993441
2025 NRG1/PDGFC loop between fibroblasts and cancer cells drives paclitaxel resistance via ferroptosis suppression in breast cancer. Cell death discovery 0 41213930
2024 Identification of a novel mutation of Platelet-Derived Growth Factor-C (PDGFC) gene in a girl with Non-Syndromic cleft lip and palate. Gene 0 38432532
2023 Identification of a Novel Variant of PDGFC Associated with Nonsyndromic Cleft Lip and Palate in a Chinese Family. International journal of genomics 0 37779880

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