Affinage

PDGFD

Platelet-derived growth factor D · UniProt Q9GZP0

Length
370 aa
Mass
42.8 kDa
Annotated
2026-04-29
90 papers in source corpus 34 papers cited in narrative 34 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PDGF-D is a secreted growth factor that functions as a major activator of PDGFR-β signaling to drive mesenchymal cell proliferation, migration, fibrosis, angiogenesis, and immune cell recruitment. It is produced as an inactive disulfide-linked homodimer (PDGF-DD) with an N-terminal CUB prodomain that sterically blocks receptor engagement at the D2/D3 domains of PDGFR-β; extracellular proteolytic cleavage by plasmin, uPA, or matriptase releases the active growth factor domain dimer, while matriptase can further generate a dominant-negative hemidimer intermediate (PMID:11331881, PMID:25678707, PMID:35777468, PMID:34236404). Active PDGF-DD signals primarily through PDGFR-β and secondarily through PDGFR-α, engaging NRP1 as a co-receptor via its C-terminal arginine, and activating PI3K/AKT, ERK1/2, JNK, p38, and STAT3 cascades to promote fibroblast and smooth muscle cell expansion, extracellular matrix deposition, epithelial-mesenchymal transition, and vascular pericyte recruitment (PMID:11331882, PMID:17397961, PMID:28254885, PMID:36792607). PDGF-D also serves as a noncanonical ligand for NKp44 on human ILC3s and signals through PDGFR-β on murine ILC3s to promote IL-22 production and intestinal immunity, and it is selectively expressed by human radial glia where it drives cortical progenitor proliferation (PMID:41758927, PMID:25391964).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2001 High

    Identification of PDGF-D as a new PDGFR-β ligand resolved a long-standing gap in the PDGF family by showing that PDGF-DD is secreted as an inactive homodimer requiring proteolytic processing to bind and activate PDGFR-β, and can also engage PDGFR-α/β heterodimers.

    Evidence Recombinant protein expression, receptor binding/activation assays, genomic mapping (two independent labs published concurrently)

    PMID:11331881 PMID:11331882 PMID:11342471

    Open questions at the time
    • Identity of physiologically relevant activating proteases was unknown
    • No structural model of prodomain-mediated autoinhibition
    • Receptor specificity on cells co-expressing both PDGFRs not fully resolved
  2. 2003 High

    PDGF-D was established as a potent mitogen and fibrogenic factor, activating ERK1/2, JNK, p38, and AKT downstream of PDGFR-β in hepatic stellate cells and transforming NIH/3T3 cells, demonstrating oncogenic and pro-fibrotic potential.

    Evidence Stable transfection/nude mouse tumorigenesis, signaling pathway Western blots, mesangial cell proliferation assays, neutralizing antibody (CR002) in rat nephritis model

    PMID:12629513 PMID:12937299 PMID:17397961

    Open questions at the time
    • In vivo activating proteases still unidentified
    • Relative contribution versus PDGF-B in fibrosis not delineated
    • Downstream transcriptional programs not mapped
  3. 2004 High

    In vivo gain-of-function studies demonstrated that PDGF-D recruits macrophages, promotes vessel maturation, and specifically causes mesangial proliferative glomerulopathy through PDGFR-β, distinguishing its biology from PDGF-C.

    Evidence Transgenic/adenoviral overexpression in mice, histology, interstitial fluid pressure measurement

    PMID:14747375 PMID:15271796

    Open questions at the time
    • Loss-of-function genetic evidence still lacking
    • Mechanism of macrophage recruitment (direct vs. indirect) unclear
  4. 2006 High

    Long-term PDGF-D neutralization in progressive glomerulonephritis proved that PDGF-D drives renal scarring including glomerulosclerosis, tubulointerstitial fibrosis, and podocyte damage, establishing therapeutic relevance.

    Evidence 8-week CR002 antibody treatment in uninephrectomized anti-Thy1.1 rat model with multiple histological readouts

    PMID:16510766

    Open questions at the time
    • Whether PDGF-D inhibition reverses established fibrosis was not tested
    • Human translation not established
  5. 2014 High

    Discovery of species-specific PDGFD expression in human radial glia expanded PDGF-D's role beyond mesenchymal biology, showing it drives cortical progenitor proliferation and may have contributed to human neocortical expansion.

    Evidence Transcriptional profiling of sorted radial glia, pharmacological inhibition in human cortical slices, in utero electroporation in mouse

    PMID:25391964

    Open questions at the time
    • Downstream transcriptional targets in radial glia not identified
    • Whether PDGF-D is sufficient for cortical expansion in non-human primates untested
  6. 2015 High

    The proteolytic activation mechanism was biochemically resolved: matriptase performs stepwise cleavage of PDGF-DD generating a dominant-negative hemidimer intermediate before releasing the active GFD dimer, with a critical R340R341 cleavage site overlapping the PDGFR-β binding interface; NRP1 was identified as a PDGF-D-specific co-receptor binding via the C-terminal arginine.

    Evidence In vitro matriptase reconstitution with mutagenesis, Co-IP of PDGFR-β–NRP1 complex, C-terminal Arg mutagenesis, ex vivo sprouting assay

    PMID:25678707 PMID:28254885

    Open questions at the time
    • Crystal structure of PDGF-D GFD or CUB domain not determined
    • Whether NRP1 co-receptor function alters downstream signaling quality unknown
    • Hemidimer function in vivo not confirmed
  7. 2016 High

    Genetic knockout of Pdgfd confirmed its non-redundant role in renal fibrosis, showing reduced PDGFR-β/p38 signaling in two independent injury models and establishing PDGF-D as a bona fide fibrogenic driver in vivo.

    Evidence Pdgfd KO mice in UUO and IRI models, adenoviral gain-of-function, phosphoprotein analysis

    PMID:26924050

    Open questions at the time
    • Combined Pdgfd/Pdgfb genetic studies not performed
    • Whether PDGF-D drives fibrosis in lung, liver, or heart by the same mechanism untested at KO level
  8. 2016 Medium

    PDGF-D was placed in multiple disease-relevant signaling circuits: activating STAT3/FAK to confer BRAF-inhibitor resistance in melanoma, upregulating androgen receptor for radioresistance in prostate cancer, and mediating neuroinflammation after intracerebral hemorrhage via plasmin-dependent activation.

    Evidence siRNA screening and epistasis in melanoma, nuclear AR fractionation in prostate cells, mouse ICH model with siRNA and Gleevec

    PMID:26732854 PMID:27302678 PMID:27671679

    Open questions at the time
    • Each disease link from single lab
    • Direct PDGF-D–STAT3 connection versus indirect via PDGFR-β not fully resolved
    • Clinical relevance of PDGF-D in drug resistance untested
  9. 2021 High

    Macrophage-derived uPA was identified as a physiologically relevant activating protease for PDGF-D in cardiac remodeling, and HIF1α was shown to directly bind the PDGFD promoter to create a feedforward loop with PDGFR-α/AKT signaling in glioblastoma.

    Evidence Adipocyte-specific Pdgfd KO and uPA bone-marrow KD in obese mice; ChIP and CRISPR KO in GBM cells with intracranial xenograft

    PMID:34236404 PMID:34470658

    Open questions at the time
    • Whether uPA is the dominant activating protease across tissues remains open
    • PDGFR-α versus PDGFR-β signaling quality downstream of PDGF-D in GBM not distinguished
  10. 2022 High

    The structural basis of prodomain autoinhibition was elucidated: the CUB domain sterically blocks PDGFR-β D2/D3 recognition of the growth factor domain, explaining why proteolytic removal is required, with differential inhibitory specificity for PDGF-D versus PDGF-B-induced proliferation.

    Evidence Structural modeling with mutagenesis-supported transphosphorylation and proliferation assays

    PMID:35777468

    Open questions at the time
    • No experimental crystal/cryo-EM structure of full-length PDGF-DD
    • Prodomain interactions with ECM components not characterized
  11. 2023 High

    PDGFD was connected to coronary artery disease risk through FOXC1/C2-dependent transcription at the rs2019090 locus, with Pdgfd knockdown reducing SMC chondromyocyte transition and macrophage-recruiting chemokine expression in atherosclerosis.

    Evidence Fine-mapping, ChIP, Pdgfd KD in SMC lineage-tracing atherosclerosis mouse model, scRNA-seq

    PMID:36792607

    Open questions at the time
    • Whether the CAD SNP effect is fully mediated through PDGFD or includes neighboring genes not excluded
    • Human vascular cell validation limited
  12. 2025 High

    PDGF-D was discovered to be a noncanonical ligand for NKp44 on human ILC3s and to signal through PDGFR-β on ILC3s in mice, promoting IL-22-dependent intestinal immunity; NKp44 engagement drives a distinct type-1 effector programme, revealing an unexpected immunological role.

    Evidence PDGFR-β conditional KO in ILC3s, NKp44 transgenic mice, PDGF-D reporter mice, enteric infection models

    PMID:41758927

    Open questions at the time
    • Whether PDGF-D–NKp44 interaction is direct or requires co-receptor not fully resolved
    • Relevance to human IBD or intestinal infection not tested clinically
    • Signaling downstream of NKp44 upon PDGF-D engagement not mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the atomic structure of full-length PDGF-DD and its receptor complexes, the tissue-specific hierarchy of activating proteases, the functional distinction between PDGFR-α- and PDGFR-β-mediated signaling downstream of PDGF-D, and whether therapeutic PDGF-D modulation can translate to human fibrotic, cardiovascular, or immune diseases.
  • No experimental high-resolution structure of PDGF-DD or CUB domain
  • Tissue-specific protease hierarchy unresolved
  • Clinical translation data absent

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 5 GO:0098772 molecular function regulator activity 2
Localization
GO:0005576 extracellular region 4 GO:0031012 extracellular matrix 1
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-1474244 Extracellular matrix organization 3 R-HSA-168256 Immune System 3 R-HSA-1266738 Developmental Biology 2
Partners
NRP1PDGFRAPDGFRBPLAUPLGST14
Complex memberships
PDGF-DD homodimer

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 PDGF-D is secreted as a disulphide-linked homodimer (PDGF-DD) and requires limited proteolysis for activation; upon proteolytic cleavage it becomes a specific agonistic ligand for PDGFR-β. Recombinant protein expression, biochemical characterization, receptor-binding and receptor activation assays Nature cell biology High 11331881 11331882
2001 PDGF-D binds to and activates PDGFR-β; in cells expressing both receptors it can also activate PDGFR-α, likely through PDGFR-α/β heterodimerization. Receptor-specific cell lines, DNA synthesis assay, receptor phosphorylation assay Nature cell biology High 11331881 11331882
2001 PDGFD gene maps to chromosome 11q22.3 and has a two-domain structure with an N-terminal CUB domain (encoded by exons 2–3) and a C-terminal PDGF cystine-knot growth factor homology domain (encoded by last 2 exons); proteolytic cleavage site is in exon 5. Fluorescence in situ hybridization, genomic DNA sequencing, exon structure determination Circulation High 11342471
2003 PDGF-D acts as a potent transforming growth factor for NIH/3T3 cells via PDGFR-β activation, inducing stress fibre reorganization, anchorage-independent growth, tumour formation in nude mice, and upregulation of VEGF. Stable transfection, soft agar assay, nude mouse tumour model, VEGF measurement Oncogene High 12629513
2003 PDGF-D signals through PDGFR-β to activate ERK1/2, JNK, p38 MAPK, and PKB/Akt in hepatic stellate cells and myofibroblasts, exerting mitogenic and fibrogenic effects comparable to PDGF-B. PDGFRβ autophosphorylation assay, Western blot of downstream kinases, cell proliferation and collagen assays Journal of hepatology High 17397961
2004 Full-length PDGF-D is activated in tissues and promotes macrophage recruitment, increased interstitial fluid pressure, and maturation/pericyte coating of blood vessels in vivo; combined expression with VEGF-E inhibits vascular leakiness. Transgenic mouse overexpression, adeno-associated virus vector delivery, histology, interstitial fluid pressure measurement, wound healing assay Blood High 15271796
2004 PDGF-D is a potent mesangial cell mitogen; adenoviral overexpression of PDGF-D in mice causes severe mesangial proliferative glomerulopathy via PDGFR-β engagement, whereas PDGF-C overexpression causes no measurable renal response. Adenoviral vector injection in mice, histology, in vitro mitogenicity assay Journal of the American Society of Nephrology : JASN High 14747375
2003 Neutralizing PDGF-DD with fully human monoclonal antibody CR002 reduces glomerular mesangial cell proliferation, monocyte/macrophage infiltration, and fibronectin accumulation in rat mesangioproliferative nephritis. Neutralizing antibody treatment in rat anti-Thy1.1 nephritis model, immunostaining, BrdU incorporation Journal of the American Society of Nephrology : JASN High 12937299
2006 PDGF-D antagonism by CR002 antibody in progressive glomerulonephritis reduces glomerulosclerosis, podocyte damage, tubulointerstitial fibrosis, collagen/fibronectin accumulation, and cortical macrophage infiltration, implicating PDGF-D in renal scarring. Long-term antibody treatment in uninephrectomised anti-Thy-1.1 rat model, histology, immunostaining Journal of the American Society of Nephrology : JASN High 16510766
2016 Pdgfd knockout mice show significantly reduced renal interstitial fibrosis in unilateral ureteral obstruction and ischemia/reperfusion injury models, associated with reduced PDGFR-β and p38 phosphorylation; adenoviral PDGF-D overexpression increases renal collagen deposition. Pdgfd knockout mice, adenoviral overexpression, UUO and IRI models, histology, phosphoprotein analysis Kidney international High 26924050
2015 PDGF-D binds NRP1 via its C-terminal Arg residue; PDGF-D (but not PDGF-B) stimulation induces PDGFRβ–NRP1 complex formation in fibroblasts, translocates NRP1 to cell-cell junctions in endothelial cells (independently of PDGFRβ), and can signal in trans between endothelial cells and pericytes. Co-immunoprecipitation, direct binding assay, mutagenesis of C-terminal Arg, confocal microscopy, ex vivo sprouting assay Journal of cell science High 28254885
2015 Matriptase cleaves full-length PDGF-D dimer in a stepwise manner generating a hemidimer (HD) intermediate and then the active growth factor domain dimer (GFD-D); the cleavage site is R340R341GR343A within loop III of the GFD which is critical for PDGFRβ binding; the HD acts as a dominant-negative ligand; matriptase can further cleave and inactivate GFD-D; PDGF-D dimer species differentially deposit into the extracellular matrix. In vitro matriptase cleavage assay, mutagenesis of cleavage site, receptor activation assay, ECM binding assay The Journal of biological chemistry High 25678707
2022 The PDGF-D CUB/prodomain inhibits PDGFR-β activation by sterically blocking D2/D3 receptor domains from recognizing the growth factor domain; the prodomain inhibits both PDGF-B and PDGF-D-mediated PDGFR-β transphosphorylation but inhibits NIH 3T3 cell proliferation induced by PDGF-D but not by PDGF-B, demonstrating differential inhibitory specificity. Structural modeling, in vitro PDGFR-β transphosphorylation assay, cell proliferation assay, prodomain inhibition experiments Journal of molecular biology High 35777468
2014 PDGFD is specifically expressed by radial glia in human but not mouse neocortex; pharmacological inhibition of PDGFD–PDGFRβ signalling in human cortical slice cultures prevents cell cycle progression of radial glia; ectopic PDGFD or constitutively active PDGFRβ in mouse neocortex increases radial glia proportion and subventricular dispersion. Transcriptional profiling, pharmacological inhibition in slice culture, in utero electroporation/injection in mouse Nature High 25391964
2021 HIF1α binds the PDGFD proximal promoter and PDGFRA intron enhancers in GBM cells under normoxia/mild-hypoxia to induce their expression; PDGF-D/PDGFRα constitutively activates AKT signaling which in turn increases HIF1α protein, forming a feedforward loop; severe hypoxia abrogates PDGFRα despite enhancing PDGF-D expression. ChIP analysis, sgRNA-Cas9 knockout, RNA-seq, loss/gain-of-function assays, intracranial xenograft model Journal of experimental & clinical cancer research High 34470658
2021 Macrophage-derived urokinase plasminogen activator (uPA) activates PDGF-D by cleaving full-length PDGF-D into the active PDGF-DD form, promoting cardiac remodeling in obese hypertensive mice; adipocyte-specific PDGF-D knockout attenuates this remodeling. Adipocyte-specific KO and transgenic mice, bone marrow-specific uPA knockdown, ELISA for active PDGF-DD, Western blot The Journal of experimental medicine High 34236404
2023 FOXC1/C2 transcription factor binding at the CAD-risk SNP rs2019090 promotes PDGFD transcription; Pdgfd promotes SMC expansion, migration, and transition to chondromyocyte phenotype in atherosclerosis; Pdgfd-expressing adventitial fibroblasts and pericytes express chemokines and leukocyte adhesion molecules linked to macrophage recruitment. Fine-mapping, ChIP, Pdgfd knockdown in SMC lineage-tracing atherosclerosis mouse model, single-cell transcriptomics Nature communications High 36792607
2015 PDGF-D regulates proliferation and migration of adipose-derived stem cells (ASCs) through PI3K/Akt pathways and via mitochondrial reactive oxygen species generation and mitochondrial fission mediated by p66Shc phosphorylation; PDGF-D upregulates expression of multiple growth factors (VEGFA, FGF1, FGF5, etc.) through MAPK signalling. siRNA knockdown, pathway inhibitors, mitochondrial ROS measurement, RT-PCR, proliferation and migration assays Stem cells (Dayton, Ohio) Medium 25332166
2015 In portal myofibroblasts and hepatic stellate cells, PDGF-D binds PDGFR-α as well as PDGFR-β, inducing receptor endocytosis, PDGFR-α-specific tyrosine phosphorylation (Y754 and Y1018), and CrkII adaptor protein recruitment; a recombinant PDGFR-α-Fc chimera blocks PDGF-D signaling. Receptor phosphorylation assay, receptor endocytosis assay, CrkII pulldown, PDGFR-α-Fc inhibition Cellular signalling Medium 25819339
2016 ZIC5 transcriptionally upregulates PDGFD expression in melanoma; PDGF-D activates FAK and STAT3 to confer drug resistance; silencing ZIC5 or PDGFD enhances apoptosis under BRAF inhibition; FAK and STAT3 positively feedback to sustain ZIC5 expression. siRNA screening, microarray, Western blot, apoptosis assay, in vivo melanoma model Cancer research Medium 27671679
2016 PDGF-D (via PDGFR-β signalling) upregulates androgen receptor expression and nuclear AR translocation in PTEN-null prostate cells; AR contributes to radiation resistance; PDGF-D overexpression increases radioresistance reversed by enzalutamide. Immunoblot of nuclear/cytosolic AR fractions, RT-PCR of AR target genes, clonogenic survival assay, irradiation experiments The Prostate Medium 26732854
2016 PDGF-D–PDGFR-β signalling mediates post-ICH neuroinflammation; plasmin acts as an upstream activator of PDGF-D; PDGF-D promotes macrophage infiltration and TNF-α production; PDGFR-β inhibition reduces microglial activation and brain injury. Mouse ICH model with siRNA knockdown of PDGF-D, recombinant PDGF-D injection, PDGFR inhibitor (Gleevec), plasmin antagonist (EACA), immunostaining Experimental neurology Medium 27302678
2011 PDGF-D overexpression promotes lymph node metastasis through induction of CXCR4 expression; blockade of CXCR4 abolishes PDGF-D-induced lymph node metastasis; PDGF-D increases perivascular cell coverage and normalises tumour vessels. Stable transfection of breast cancer cells, shRNAi, imatinib treatment, orthotopic mouse model, CXCR4 blockade Clinical cancer research Medium 21459800
2012 PDGF-D released by adipose tissue-derived stem cells (ASCs) induces epithelial-mesenchymal transition (EMT) in breast cancer cells in a paracrine manner; neutralising PDGF-D antibody blocks this EMT and tumour growth. Conditioned medium experiments, neutralising antibody, Western blot for EMT markers, flow cytometry, mouse tumour model International journal of cancer Medium 22038895
2017 PDGF-D promotes EMT in colorectal cancer by upregulating Notch1 and Twist1; Notch1 overexpression rescues the effects of PDGF-D knockdown on Twist1 expression, placing PDGF-D upstream of Notch1/Twist1 axis. siRNA knockdown, plasmid overexpression, Western blot, migration assays, xenograft model Oncotarget Medium 28035069
2023 PDGFD promoter is reversibly demethylated in gemcitabine-resistant PDAC cells, increasing PDGFD expression; PDGF-D activates STAT3 in autocrine and paracrine manner to upregulate RRM1 expression, causing gemcitabine resistance. Reduced Representation Bisulfite Sequencing, demethylation experiments, STAT3 inhibition, RRM1 measurement, in vitro and in vivo resistance models Cancer letters Medium 37321532
2015 PDGF-D promotes fibroblast invasion in 3D collagen gels via PI3K, JNK, and ERK1/2 signalling pathways, inducing Snail expression which in turn upregulates MT1-MMP. 3D type I collagen invasion assay, Snail siRNA knockdown, PI3K/JNK/ERK inhibitors, Western blot and RT-PCR Tumour biology Medium 26234766
2022 PDGFD drives endothelial commitment of embryonic stem cells via the MAPK/ERK pathway; PDGFD deletion or knockdown inhibits ESC differentiation into endothelial cells and reduces blood vessel density in embryonic, neonatal, and teratoma models. Loss- and gain-of-function assays, RNA sequencing, PDGFD knockout mice, embryonic and neonatal vascular analysis Angiogenesis Medium 35859222
2024 Endothelial PDGF-D is transiently induced at ischemic stroke injury sites; increased PDGF-D bioavailability attenuates pericyte loss and fibrotic transition, promotes pericyte migration and endothelial coverage, and stimulates pro-angiogenic factor secretion, improving neurovascular recovery. Mouse ischemic stroke model, siRNA knockdown, recombinant PDGF-D administration, cell-based ischemia assays with human brain pericytes and endothelial cells Cellular and molecular life sciences Medium 38769116
2008 PDGF-D induces MMP-9 mRNA expression and enhances secretion of MMP-2 and MMP-9 in monocytes/macrophages, and promotes monocyte migration in a concentration-dependent manner. Boyden chamber migration assay, RT-PCR for MMP-9, MMP-2/9 secretion assay Atherosclerosis Medium 18573494
2018 PVAT-derived PDGF-D promotes adventitial fibroblast proliferation, migration, and inflammatory factor expression; adipocyte-specific PDGF-D transgenic mice show exacerbated aortic aneurysm formation with AngII infusion; PDGF-D inhibition reduces AA incidence. Transcriptome analysis, adipocyte-specific transgenic mice, PDGF-D function inhibition, cultured adventitial fibroblast assays Diabetes Medium 29794241
2023 miR-145-5p directly targets PDGFD mRNA (validated by luciferase reporter assay); miR-145-5p inhibition promotes wound healing in diabetic foot ulcer models through upregulation of PDGFD, which increases fibroblast viability and migration. Luciferase reporter assay, miR-145-5p mimics/inhibitors, wound healing assay, DFU mouse model Biochemical genetics Medium 37950842
2026 PDGF-D acts as a noncanonical ligand for NKp44 on human ILC3s; in mice (which lack NKp44), PDGF-D promotes IL-22 production and ILC3 proliferation through PDGFRβ; mice lacking PDGFRβ in ILC3s are susceptible to enteric infections; in NKp44-transgenic mice, PDGF-D engagement of NKp44 drives a type-1 effector programme (TNF-α and IFN-γ); fibroblasts and endothelial cells are the inflammation-responsive cellular source of PDGF-D. PDGFRβ conditional KO in ILC3s, NKp44 transgenic mice, PDGF-D reporter mice, enteric infection model, cytokine measurement Science immunology High 41758927
2025 Pdgfd–Pdgfrb signalling in pancreatic cancer promotes perineural invasion by stimulating cancer cell invasiveness, neurite outgrowth, and direct physical engagement with glia; pharmacological blockade reduces perineural invasion in vivo. Spatial transcriptomics, in vitro invasion/neurite outgrowth assays, pharmacological inhibition, in vivo PNI model bioRxivpreprint Medium 40909696

Source papers

Stage 0 corpus · 90 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 PDGF-D is a specific, protease-activated ligand for the PDGF beta-receptor. Nature cell biology 435 11331881
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 347 12097282
2001 PDGF-D, a new protease-activated growth factor. Nature cell biology 292 11331882
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
2007 Pro-fibrogenic potential of PDGF-D in liver fibrosis. Journal of hepatology 155 17397961
2004 PDGF-D induces macrophage recruitment, increased interstitial pressure, and blood vessel maturation during angiogenesis. Blood 150 15271796
2003 Novel PDGF family members: PDGF-C and PDGF-D. Cytokine & growth factor reviews 142 12651221
2014 Radial glia require PDGFD-PDGFRβ signalling in human but not mouse neocortex. Nature 135 25391964
2003 PDGF-D is a potent transforming and angiogenic growth factor. Oncogene 130 12629513
2001 Chromosomal location, exon structure, and vascular expression patterns of the human PDGFC and PDGFD genes. Circulation 104 11342471
2010 Emerging roles of PDGF-D signaling pathway in tumor development and progression. Biochimica et biophysica acta 98 20434526
2018 PDGF-C and PDGF-D signaling in vascular diseases and animal models. Molecular aspects of medicine 84 29410092
2012 Epithelial-mesenchymal transition in breast cancer lines is mediated through PDGF-D released by tissue-resident stem cells. International journal of cancer 84 22038895
2003 A fully human monoclonal antibody (CR002) identifies PDGF-D as a novel mediator of mesangioproliferative glomerulonephritis. Journal of the American Society of Nephrology : JASN 74 12937299
2018 Dermatofibrosarcoma protuberans with a novel COL6A3-PDGFD fusion gene and apparent predilection for breast. Genes, chromosomes & cancer 73 30014607
2012 Emerging roles of PDGF-D in EMT progression during tumorigenesis. Cancer treatment reviews 71 23261166
2021 Rare variant analysis of 4241 pulmonary arterial hypertension cases from an international consortium implicates FBLN2, PDGFD, and rare de novo variants in PAH. Genome medicine 69 33971972
2008 Effects of PDGF-C and PDGF-D on monocyte migration and MMP-2 and MMP-9 expression. Atherosclerosis 69 18573494
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 66 29955147
2011 PDGF-D improves drug delivery and efficacy via vascular normalization, but promotes lymphatic metastasis by activating CXCR4 in breast cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 66 21459800
2017 PDGF-D promotes cell growth, aggressiveness, angiogenesis and EMT transformation of colorectal cancer by activation of Notch1/Twist1 pathway. Oncotarget 63 28035069
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
2015 Functional regulation of adipose-derived stem cells by PDGF-D. Stem cells (Dayton, Ohio) 61 25332166
2003 Obstructive uropathy in mice and humans: potential role for PDGF-D in the progression of tubulointerstitial injury. Journal of the American Society of Nephrology : JASN 59 14514732
2006 Antagonism of PDGF-D by human antibody CR002 prevents renal scarring in experimental glomerulonephritis. Journal of the American Society of Nephrology : JASN 58 16510766
2016 Role of PDGF-D and PDGFR-β in neuroinflammation in experimental ICH mice model. Experimental neurology 57 27302678
2007 PDGF-D inhibition by CR002 ameliorates tubulointerstitial fibrosis following experimental glomerulonephritis. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 56 17308324
2013 Chemoresistance to gemcitabine in hepatoma cells induces epithelial-mesenchymal transition and involves activation of PDGF-D pathway. Oncotarget 55 24158561
2009 PDGF-D signaling: a novel target in cancer therapy. Current drug targets 53 19149534
2004 Exogenous PDGF-D is a potent mesangial cell mitogen and causes a severe mesangial proliferative glomerulopathy. Journal of the American Society of Nephrology : JASN 52 14747375
2020 Genomic analysis of worldwide sheep breeds reveals PDGFD as a major target of fat-tail selection in sheep. BMC genomics 51 33203382
2021 The HIF1α-PDGFD-PDGFRα axis controls glioblastoma growth at normoxia/mild-hypoxia and confers sensitivity to targeted therapy by echinomycin. Journal of experimental & clinical cancer research : CR 48 34470658
2018 Perivascular Adipose Tissue-Derived PDGF-D Contributes to Aortic Aneurysm Formation During Obesity. Diabetes 48 29794241
2016 The role of PDGF-D in healthy and fibrotic kidneys. Kidney international 48 26924050
2017 Neuropilin 1 binds PDGF-D and is a co-receptor in PDGF-D-PDGFRβ signaling. Journal of cell science 46 28254885
2016 ZIC5 Drives Melanoma Aggressiveness by PDGFD-Mediated Activation of FAK and STAT3. Cancer research 42 27671679
2012 A case-control study provides evidence of association for a common SNP rs974819 in PDGFD to coronary heart disease and suggests a sex-dependent effect. Thrombosis research 37 22704460
2005 PDGF-D contributes to neointimal hyperplasia in rat model of vessel injury. Biochemical and biophysical research communications 33 15752751
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
2010 RNAi-mediated inhibition of PDGF-D leads to decreased cell growth, invasion and angiogenesis in the SGC-7901 gastric cancer xenograft model. Cancer biology & therapy 27 20087065
2023 Molecular mechanisms of coronary artery disease risk at the PDGFD locus. Nature communications 26 36792607
2021 PDGF-D activation by macrophage-derived uPA promotes AngII-induced cardiac remodeling in obese mice. The Journal of experimental medicine 24 34236404
2002 The expression of SCDGF/PDGF-C/fallotein and SCDGF-B/PDGF-D in the rat central nervous system. Mechanisms of development 21 11850188
2019 Possible Role and Therapeutic Target of PDGF-D Signalling in Colorectal Cancer. Cancer investigation 20 30836770
2020 Verification and Analysis of Sheep Tail Type-Associated PDGF-D Gene Polymorphisms. Animals : an open access journal from MDPI 19 31935823
2024 Endothelial PDGF-D contributes to neurovascular protection after ischemic stroke by rescuing pericyte functions. Cellular and molecular life sciences : CMLS 18 38769116
2021 Novel TNC-PDGFD fusion in fibrosarcomatous dermatofibrosarcoma protuberans: a case report. Diagnostic pathology 18 34256767
2023 Reversible promoter demethylation of PDGFD confers gemcitabine resistance through STAT3 activation and RRM1 upregulation. Cancer letters 17 37321532
2014 PDGF-D expression is down-regulated by TGFβ in fibroblasts. PloS one 15 25280005
2021 Downregulation of PDGF-D Inhibits Proliferation and Invasion in Breast Cancer MDA-MB-231 Cells. Clinical breast cancer 14 34272173
2007 The role of PDGF-D in mesangioproliferative glomerulonephritis. Contributions to nephrology 14 17495455
2024 Breast cancer stem cell-derived exosomal lnc-PDGFD induces fibroblast-niche formation and promotes lung metastasis. Oncogene 13 39633064
2001 Molecular cloning of SCDGF-B, a novel growth factor homologous to SCDGF/PDGF-C/fallotein. Biochemical and biophysical research communications 13 11162582
2017 DNA Methylation of the PDGFD Gene Promoter Increases the Risk for Intracranial Aneurysms and Brain Arteriovenous Malformations. DNA and cell biology 12 28346846
2020 PDGFD induces ibrutinib resistance of diffuse large B‑cell lymphoma through activation of EGFR. Molecular medicine reports 11 32186759
2006 Expression and localization of PDGF-B, PDGF-D, and PDGF receptor in the kidney of angiotensin II-infused rat. Laboratory investigation; a journal of technical methods and pathology 11 17043664
2024 Exploring the impact of PDGFD in osteosarcoma metastasis through single-cell sequencing analysis. Cellular oncology (Dordrecht, Netherlands) 10 38652223
2022 Short variation of the sheep PDGFD gene is correlated with litter size. Gene 10 35985413
2021 Repurposing bortezomib for choroidal neovascularization treatment via antagonizing VEGF-A and PDGF-D mediated signaling. Experimental eye research 10 33476605
2015 Dynamic regulation of platelet-derived growth factor D (PDGF-D) activity and extracellular spatial distribution by matriptase-mediated proteolysis. The Journal of biological chemistry 10 25678707
2022 circ-0007707/miR-429/PDGFD Pathway Regulates the Progression of Gastric Cancer by Modulating the Immune-Gene Signature. Journal of oncology 9 35509844
2016 The interaction between androgen receptor and PDGF-D in the radiation response of prostate carcinoma. The Prostate 9 26732854
2023 Insertion/Deletion (InDel) Variants within the Sheep Fat-Deposition-Related PDGFD Gene Strongly Affect Morphological Traits. Animals : an open access journal from MDPI 8 37174523
2022 PDGFD switches on stem cell endothelial commitment. Angiogenesis 8 35859222
2016 PDGF-D gene polymorphism is associated with increased cardiovascular mortality in elderly men. BMC medical genetics 7 27585990
2003 A novel murine PDGF-D splicing variant results in significant differences in peptide expression and function. Biochemical and biophysical research communications 7 12890490
2023 lncRNA PITPNA-AS1 promotes cell proliferation and metastasis in hepatocellular carcinoma by upregulating PDGFD. Aging 6 37253627
2022 Combination therapy with chitosan/siRNA nanoplexes targeting PDGF-D and PDGFR-β reveals anticancer effect in breast cancer. The journal of gene medicine 6 36413571
2023 MicroRNA miR-145-5p Inhibits Cutaneous Wound Healing by Targeting PDGFD in Diabetic Foot Ulcer. Biochemical genetics 5 37950842
2022 PDGF-D Prodomain Differentially Inhibits the Biological Activities of PDGF-D and PDGF-B. Journal of molecular biology 5 35777468
2025 Dermatofibrosarcoma protuberans with PDGFD rearrangements: a case series featuring a novel EMILIN1::PDGFD fusion and comprehensive literature review. Virchows Archiv : an international journal of pathology 4 40167642
2021 Inhibiting PDGF-D alleviates the symptoms of HELLP by suppressing NF-κB activation. Journal of molecular endocrinology 4 33640869
2021 New αIIbβ3 variants in 28 Turkish Glanzmann patients; structural hypothesis for complex activation by residues variations in I-EGF domains. Platelets 4 34275420
2018 Effects of 3-Tetrazolyl Methyl-3-Hydroxy-Oxindole Hybrid (THOH) on Cell Proliferation, Apoptosis, and G2/M Cell Cycle Arrest Occurs by Targeting Platelet-Derived Growth Factor D (PDGF-D) and the MEK/ERK Signaling Pathway in Human Lung Cell Lines SK-LU-1, A549, and A-427. Medical science monitor : international medical journal of experimental and clinical research 4 29961751
2015 PDGF-D promotes dermal fibroblast invasion in 3-dimensional extracellular matrix via Snail-mediated MT1-MMP upregulation. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 4 26234766
2025 Comprehensive Clinicopathological and Multiomics Characterization of Dermatofibrosarcoma Protuberans Revealed PDGFD Fusion as Distinct Molecular Subtype With Better Survival. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 3 40348059
2025 EGR1 Promotes Craniofacial Bone Regeneration via Activation of ALPL⁺PDGFD⁺ Periosteal Stem Cells. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 3 40650643
2024 The role of THBS1 and PDGFD in the immune microenvironment of Helicobacter pylori-associated gastric cancer. Arab journal of gastroenterology : the official publication of the Pan-Arab Association of Gastroenterology 2 38705811
2025 Effect of HepG2-Derived Exosome with PDGF-D Knockdown on Transformation of Normal Fibroblasts into Tumor-Associated Fibroblasts in Liver Cancer. Frontiers in bioscience (Landmark edition) 1 40152369
2023 Molecular mechanisms of coronary artery disease risk at the PDGFD locus. bioRxiv : the preprint server for biology 1 36747745
2021 Retracted: Effects of 3-Tetrazolyl Methyl-3-Hydroxy-Oxindole Hybrid (THOH) on Cell Proliferation, Apoptosis, and G2/M Cell Cycle Arrest Occurs by Targeting Platelet-Derived Growth Factor D (PDGF-D) and the MEK/ERK Signaling Pathway in Human Lung Cell Lines SK-LU-1, A549, and A-427. Medical science monitor : international medical journal of experimental and clinical research 1 33762562
2015 A study on the association of rs7950273 polymorphism in the PDGFD with ischaemic stroke in the Chinese Han population. Annals of human biology 1 26362023
2026 Novel FGL2::PDGFD and TGFBI::PDGFB Fusions Expand the Molecular Spectrum of Dermatofibrosarcoma Protuberans. Genes, chromosomes & cancer 0 41711154
2026 Divergent ILC3 responses to PDGF-D control mucosal immunity. Science immunology 0 41758927
2026 PDGFD maintains ovine tail ADSCs in a proliferative state by suppressing CXCL8 and activating PI3K/MAPK signaling. Frontiers in veterinary science 0 41767679
2026 PDGFD: A Dual-Function Regulator That Maintains Myoblast Pool and Fuels Myogenic Differentiation. Current issues in molecular biology 0 41899473
2025 PDGF-D Promotes Epithelial-Mesenchymal Transition of Glioma Cells Through the NF-κB/NOTCH1 Pathway. Cancer medicine 0 40530904
2025 The Pdgfd-Pdgfrb axis orchestrates tumor-nerve crosstalk in pancreatic cancer. bioRxiv : the preprint server for biology 0 40909696
2024 PDGF-D Is Dispensable for the Development and Progression of Murine Alport Syndrome. The American journal of pathology 0 38309427
2024 CCL28 promotes progression of hepatocellular carcinoma through PDGFD-regulated MMP9 and VEGFA pathways. Discover oncology 0 39085670