| 1983 |
PDGF B-chain shares virtual amino acid sequence identity (~104 residues) with the predicted transforming protein p28sis of simian sarcoma virus (SSV), establishing that the v-sis oncogene encodes a PDGF-related protein. |
Amino acid sequencing of purified PDGF and comparison with predicted v-sis protein sequence |
Nature |
High |
6306471
|
| 1984 |
The c-sis proto-oncogene encodes a polypeptide precursor of the PDGF B chain, with amino acid sequence identity over 109 residues confirmed by direct sequencing; the PDGF A chain is ~60% homologous to the B chain but encoded at a separate locus. |
Nucleotide sequencing of c-sis genomic clones combined with amino acid sequence analysis of purified PDGF B chain |
The EMBO journal |
High |
6329745
|
| 1984 |
SSV-transformed cells secrete a PDGF-like protein (p28v-sis) that stimulates autocrine cell growth through PDGF receptors; anti-PDGF antisera block 3H-thymidine incorporation in growing SSV-transformed cells; PDGF receptors purified from SSV-NIH 3T3 cells retain active protein tyrosine kinase activity stimulated by PDGF. |
Mitogenic assay, 125I-PDGF receptor competition binding, anti-PDGF antisera neutralization, receptor purification with tyrosine kinase assay, tumor growth in nude mice |
Cell |
High |
6091918
|
| 1984 |
Expression of the normal human sis/PDGF-2 coding sequence under retroviral LTR control induces cellular transformation of NIH-3T3 cells, demonstrating that the growth factor coding sequence itself has transforming activity. |
Stable transfection of chimeric LTR-c-sis construct into NIH/3T3 cells; transforming foci assay; detection of sis/PDGF-2 translational products |
Cell |
High |
6091919
|
| 1984 |
The v-sis gene product competes with 125I-PDGF for receptor binding on fibroblast membranes, directly demonstrating functional equivalence between the SSV oncogene product and PDGF. |
Bacterial expression of v-sis protein; 125I-PDGF receptor competition binding assay; immunochemical identification |
The Journal of biological chemistry |
High |
6088510
|
| 1985 |
The v-sis gene product specifically binds PDGF receptors, stimulates tyrosine phosphorylation of PDGF receptors, and induces DNA synthesis in quiescent fibroblasts; transformation by SSV correlates strictly with PDGF receptor expression in target cells. |
Partial purification of v-sis protein; receptor binding; tyrosine phosphorylation assay; mitogenic assay; antibody neutralization; cell susceptibility correlation |
Science (New York, N.Y.) |
High |
2996133
|
| 1985 |
Normal human endothelial cells in culture express PDGF B chain mRNA and synthesize a PDGF-B precursor polypeptide (predicted Mr 27,281), establishing endothelial cells as a physiological source of PDGF-B. |
cDNA cloning and complete sequence analysis of sis-homologous cDNA from human umbilical vein endothelial cells |
Nature |
High |
4033772
|
| 1986 |
The SIS/PDGF2 mRNA is 3373 nucleotides with only a 723-bp coding sequence flanked by long 5' (1022 bp) and 3' (1625 bp) untranslated regions; a TATA box 24 bp upstream and an enhancer-like TG element downstream of the polyadenylation site were identified as putative regulatory elements. |
cDNA cloning, nuclease S1 mapping, primer extension, and nucleotide sequence analysis |
Proceedings of the National Academy of Sciences of the United States of America |
High |
3517869
|
| 1986 |
The v-sis gene product is co-translationally processed in the endoplasmic reticulum–Golgi compartment where signal sequence cleavage and N-linked glycosylation occur; it contains no transmembrane regions (confirmed by trypsin protection in microsomes); mutation of the proposed proteolytic processing site (Lys-Arg→Asn-Ser at residues 110–111) retains full biological activity; mutations disrupting the signal sequence cause nuclear mislocation and loss of activity. |
Site-directed mutagenesis; subcellular fractionation; microsome trypsin protection assay; N-linked glycosylation analysis |
Molecular and cellular biology |
High |
3537701
|
| 1986 |
Phorbol ester (TPA) induces c-sis/PDGFB gene transcription in K-562 hematopoietic stem cells during megakaryoblastic differentiation, as determined by nuclear run-off transcriptional assay, without generalized effects on other hematopoietic cell lines. |
Northern blot analysis; nuclear run-off transcriptional assay |
Molecular and cellular biology |
Medium |
3466024
|
| 1987 |
Each of the eight conserved cysteine residues in the v-sis/PDGF-B molecule is required for disulfide-linked dimer formation; however, interchain disulfide bonds are not essential for receptor activation—only the four cysteines forming intramolecular disulfide bonds are required for biological activity. |
Site-directed mutagenesis of individual cysteine codons; disulfide dimer formation assay; transforming activity assay |
Science (New York, N.Y.) |
High |
3035718
|
| 1989 |
Transformation by v-sis occurs through internal activation of PDGF receptors before cell surface expression: a v-sis mutant encoding ER/Golgi-retained protein transforms NRK cells as efficiently as wild-type without secreting detectable v-sis protein, and anti-PDGF antisera fail to reverse morphological transformation. |
Construction of ER/Golgi-retention mutant of v-sis; stable transfection; transformation assay; anti-PDGF antibody treatment |
Science (New York, N.Y.) |
High |
2551043
|
| 1989 |
PDGF-B induces a SIF (sis-inducible factor) DNA-binding activity that binds a conserved element upstream of the c-fos promoter; this SIF-binding element confers sis/PDGF inducibility onto a truncated c-fos promoter and functions additively with the serum response element (SRE), but only responds to sis/PDGF (not phorbol esters or serum). |
Electrophoretic mobility shift assay; reporter gene transfection; promoter deletion analysis with recombinant PDGF |
The EMBO journal |
High |
2176154
|
| 1989 |
Internal activation of PDGF receptors by v-sis product is sufficient for transformation, but activated receptors must reach the cell surface to couple with intracellular mitogenic signaling; suramin completely blocks proliferation and eliminates cell-surface receptor tyrosine phosphorylation without affecting intracellular receptor phosphorylation. |
Suramin treatment; anti-PDGF neutralizing antibody; tyrosine phosphorylation assay of cell-surface vs. intracellular PDGF receptors; defined medium proliferation assay |
Proceedings of the National Academy of Sciences of the United States of America |
High |
2813378
|
| 1989 |
PDGF-B mRNA and protein expression in glioblastoma: proliferating vascular endothelial cells in human glioblastoma coexpress PDGF B chain mRNA and PDGF receptor mRNA, supporting an autocrine growth stimulation mechanism for endothelial hyperplasia in this tumor. |
RNA transfer blot analysis; in situ hybridization of tumor biopsies |
Proceedings of the National Academy of Sciences of the United States of America |
Medium |
2845420
|
| 1989 |
TGF-β and phorbol ester (PMA/diacylglycerol via protein kinase C) each induce c-sis/PDGF-B mRNA expression in glioblastoma cells through distinct signaling routes (TGF-β uses a PKC-independent kinase pathway); both pathways converge on transcriptional activation of c-sis. |
Nuclear run-on transcription assay; PKC downregulation; kinase inhibitor H7; cycloheximide treatment; RNA hybridization |
Cancer research |
Medium |
2655888
|
| 1990 |
PDGF-B protein is localized within macrophages in all stages of human and nonhuman primate atherosclerotic lesion development, implicating macrophage-derived PDGF-B as a source of chemotactic and growth-stimulatory signals for intimal smooth muscle cells. |
Immunohistochemical localization of PDGF-B protein in atherosclerotic tissue sections |
Science (New York, N.Y.) |
Medium |
2343305
|
| 1991 |
Two specific PDGF-B chain residues, arginine 27 and isoleucine 30, mediate receptor binding and cell activation; substitutions at these positions create PDGF-B mutants defective in receptor affinity and mitogenic activity without disrupting overall protein structure (confirmed by circular dichroism and fluorescence spectroscopy). |
Site-directed mutagenesis; 125I-PDGF-BB displacement assay; mitogenic assay; inositol lipid turnover; circular dichroism; fluorescence spectroscopy |
The EMBO journal |
High |
1661670
|
| 1992 |
SPARC (extracellular glycoprotein) specifically binds PDGF-BB and PDGF-AB dimers (but not PDGF-AA) and inhibits their binding to PDGF receptors on dermal fibroblasts in a dose-dependent and pH-dependent manner. |
Specific immunoprecipitation of SPARC–125I-PDGF-BB complexes; solid-phase binding assay; receptor competition binding assay; pH-dependence analysis |
Proceedings of the National Academy of Sciences of the United States of America |
High |
1311092
|
| 1992 |
The p85 regulatory subunit of PI 3-kinase associates with the PDGF receptor via its SH2 domains in a tyrosine autophosphorylation-dependent manner; binding requires receptor kinase activity and the N-terminal SH2 domain binds PDGF receptors more stably than EGF receptors. |
Co-immunoprecipitation; GST-SH2 fusion protein binding assays; phosphotyrosine inhibition assays; Western blot |
Molecular and cellular biology |
High |
1372091
|
| 1993 |
A 10-bp element named SPE (SIS proximal element, positions -58 to -39 relative to PDGF-B mRNA start site) is essential for TPA-induced transcriptional activation of the SIS/PDGFB promoter in megakaryocytes; gel shift assays show a TPA-inducible nuclear complex that forms over the same time frame as mRNA induction and is blocked by cycloheximide, indicating requirement for new protein synthesis. |
Linker scanning mutagenesis across 250-bp promoter; luciferase reporter assay; gel mobility-shift assay; time-course analysis; cycloheximide treatment |
Proceedings of the National Academy of Sciences of the United States of America |
High |
8356057
|
| 1994 |
v-sis-induced Egr-1 expression is mediated by a pathway requiring tyrosine kinase activity and c-Ha-Ras; dominant-negative Ras and Raf mutants abrogate Egr-1 induction by v-sis/PDGF-B, and this signal is independent of protein kinase C. |
Conditional metallothionein-v-sis expression system; dominant-negative Ras and Raf transfection; Egr-1 promoter-reporter assay; PKC inhibition |
Journal of cellular biochemistry |
Medium |
7890805
|
| 1994 |
Selective PDGF receptor kinase blockers (tyrphostins AG1295 and AG1296) reverse the transformed phenotype of sis-transfected NIH 3T3 cells without affecting src-transformed cells or c-src kinase activity, confirming that PDGF receptor kinase activity is required for v-sis/PDGF-B-driven transformation. |
Tyrphostin treatment; transformation reversal assay; receptor autophosphorylation assay; kinase activity assay; selectivity profiling against multiple receptors |
Cancer research |
High |
7954456
|
| 1995 |
Mechanical strain-induced fetal lung cell growth is mediated by upregulation of PDGF-B and PDGF-β receptor mRNA and protein; phosphorothioate antisense PDGF-B oligonucleotides, neutralizing PDGF-BB antibody, and the PDGF receptor tyrosine kinase inhibitor tyrphostin 9 each abolish strain-induced DNA synthesis. |
Antisense oligonucleotide knockdown; neutralizing antibody; tyrosine kinase inhibitor; DNA synthesis assay; mRNA and protein expression analysis |
The American journal of physiology |
Medium |
7653578
|
| 1997 |
In dermatofibrosarcoma protuberans (DFSP), chromosomal translocation t(17;22) fuses COL1A1 to PDGFB, deleting exon 1 of PDGFB and releasing it from normal transcriptional regulation, producing constitutive PDGF-B expression that drives tumor formation. |
Genomic and RNA-level characterization of translocation breakpoints; RT-PCR; FISH |
Nature genetics |
High |
8988177
|
| 1998 |
PDGF-B knockout mice lack pericytes and mesangial cells, while PDGF-A knockout mice lack alveolar smooth muscle cells, demonstrating that PDGF-B is specifically required for the development of pericytes and mesangial cells (but not other smooth muscle cell subtypes). |
Targeted gene knockout in mice; histological analysis of pericyte and mesangial cell development |
Current opinion in nephrology and hypertension |
High |
9442358
|
| 1998 |
PDGF signals through Ras/PI3K/Akt/IKK to activate NF-κB, which transmits both a proliferative signal (via c-myc induction) and an anti-apoptotic signal that counterbalances c-Myc cytotoxicity; Akt transiently associates in vivo with IKK and induces IKK activation upon PDGF stimulation. |
Co-immunoprecipitation of Akt–IKK complex; kinase assays; dominant-negative constructs; NF-κB reporter assays; apoptosis assays |
Nature |
High |
10485711
|
| 1998 |
PDGF receptor dimerization induced by ligand binding leads to autophosphorylation, enabling recruitment and activation of cytoplasmic SH2-domain-containing signal transduction molecules (including PI3K, PLCγ, Src family kinases, Grb2, SHP-2), initiating pathways controlling cell growth, actin reorganization, migration, and differentiation. |
Biochemical analysis of receptor phosphorylation; SH2 domain binding studies; downstream signaling assays |
Biochimica et biophysica acta |
High |
9739761
|
| 1999 |
Cyclic mechanical strain increases PDGF-B mRNA and activates the PDGF-B promoter (12-fold in psisCAT 6A construct), and also upregulates PDGF-β receptor protein, both contributing to strain-induced smooth muscle cell proliferation; neutralizing antibodies to PDGF-β receptor reduce strain-induced thymidine incorporation by 50%. |
Cyclic strain on silicone elastomer; promoter-CAT reporter transfection; neutralizing antibody; Western blot; 3H-thymidine incorporation |
Biochemical and biophysical research communications |
Medium |
10558917
|
| 2001 |
The COL1A1-PDGFB chimeric protein produced in DFSP is processed in transfected cells into mature PDGF-B dimers that activate the PDGFB receptor pathway in a paracrine manner, rendering cells growth-factor-independent and tumorigenic; mutagenesis of the COL1A1-PDGFB cleavage site shows that even uncleaved forms retain mitogenic activity. |
Stable and transient transfection; anti-PDGFB antibody detection; growth factor independence assay; nude mouse tumorigenicity assay; site-directed mutagenesis of processing site |
Oncogene |
High |
11420709
|
| 2001 |
PDGF-B is expressed by cultured human endothelial cells and kidney epithelial cells (BSC-1), which secrete a PDGF-like protein with mitogenic and chemotactic activities inhibitable by anti-PDGF antibody; c-sis but not c-sis A-chain mRNA is detected in these cells, and TGF-β2 induces c-sis mRNA accumulation without corresponding increase in secreted PDGF-like activity. |
Northern blot with c-sis cDNA probe; mitogenic and chemotactic activity assays; antibody inhibition; protein secretion measurement |
The American journal of physiology |
Medium |
3177660
|
| 2002 |
Adiponectin specifically binds PDGF-BB (but not PDGF-AA) and inhibits PDGF-BB binding to smooth muscle cells, suppressing PDGF-β receptor autophosphorylation and ERK phosphorylation, thereby inhibiting PDGF-BB-driven smooth muscle cell proliferation and migration. |
125I-PDGF-BB binding competition; immunoblot of receptor autophosphorylation and ERK phosphorylation; proliferation (3H-thymidine) and migration (Boyden chamber) assays |
Circulation |
High |
12070119
|
| 2003 |
Endothelial PDGF-B retention motif (heparan sulfate proteoglycan-binding domain) is required for proper pericyte integration into the vessel wall in tumors; loss of this retention motif (pdgf-b ret/ret mice) causes pericyte detachment and partial loss, increased vessel diameter, and hemorrhaging even when PDGF-B is provided by tumor cells. |
Mouse genetics (pdgf-b ret/ret); tumor transplantation; transgenic PDGF-B expression; pericyte coinjection with tumor cells; histological and vascular analysis |
The Journal of clinical investigation |
High |
14561699
|
| 2005 |
PDGF-B signaling via the MAPK pathway induces YB-1 subcellular shuttling from nucleus to cytoplasm in mesangial cells during mesangioproliferative glomerulonephritis; YB-1 knockdown by RNAi abolishes the mitogenic effect of PDGF-B, identifying YB-1 as a necessary downstream signaling target. |
PDGF-B infusion in vivo; PDGF aptamer blockade; MEK inhibitor U0126; RNAi knockdown; immunolocalization; in vitro proliferation assay |
Journal of the American Society of Nephrology : JASN |
High |
16093451
|
| 2005 |
Hypoxia increases endothelial PDGF-B mRNA and protein via a transcriptional mechanism; hypoxic mesangial cells show 2–3-fold enhanced proliferative response to PDGF-B associated with increased specific receptor binding capacity; hypoxic conditioned medium chemoattractant activity is largely abolished by PDGF-B neutralizing antibody. |
Northern and Western blot; saturation binding assay; 3H-thymidine proliferation; Boyden chamber migration; neutralizing antibody |
Kidney international |
Medium |
16014047
|
| 2007 |
TGF-β-Smad pathway promotes glioma cell proliferation by transcriptionally inducing PDGF-B expression in gliomas with an unmethylated PDGF-B gene; the epigenetic methylation status of the PDGF-B gene is the molecular determinant of whether TGF-β acts as oncogenic (inducing PDGF-B and proliferation) or not in human glioma. |
Transcriptomic profiling; ChIP for Smad binding; PDGF-B promoter methylation analysis; gain/loss-of-function experiments; primary patient-derived glioma cultures |
Cancer cell |
High |
17292826
|
| 2008 |
PDGF-B/PDGFR-β signaling is required for cardiac contributions of epicardium-derived cells and cardiac neural crest; Pdgf-b-/- and Pdgfr-β-/- mouse embryos show ventricular septal defects, atrioventricular valve maldevelopment, impaired coronary arteriogenesis, myocardial hypoplasia, and cardiac nerve hypoplasia. |
Analysis of Pdgf-b-/- and Pdgfr-β-/- mouse embryos; immunohistochemical staining for αSMA, periostin, ephrinB2, VEGFR-2, NCAM at multiple embryonic stages |
Developmental dynamics |
High |
18213589
|
| 2008 |
PDGF-BB signaling transcriptionally induces miR-221, which then downregulates c-Kit and p27Kip1; loss of p27Kip1 by miR-221 drives PDGF-mediated vascular smooth muscle cell proliferation, while decreased c-Kit suppresses SMC-specific contractile gene expression via reduced Myocardin. |
miRNA expression profiling; promoter-reporter assay; miR-221 mimic/inhibitor transfection; target site mutagenesis; luciferase reporter; western blot |
The Journal of biological chemistry |
High |
19088079
|
| 2009 |
VEGF-C regulates PDGF-B expression via VEGFR3 signaling; blockade of VEGFR3 reduces PDGF-B expression and causes marked capillary dilation with mural cell dissociation; conversely, blockade of PDGF-BB diminishes VEGF-C expression, establishing a mutual regulatory loop between VEGF-C and PDGF-B in vascular stabilization. |
Neutralizing antibody AFL-4 against VEGFR3; PDGF-BB blocking antibody; murine hindlimb ischemia model; histological and blood flow analysis |
American journal of physiology. Heart and circulatory physiology |
Medium |
19734356
|
| 2011 |
SDF-1α induces PDGF-B mRNA and protein expression via a transcriptional mechanism involving ELK-1 transcription factor binding to the pdgf-b promoter; this SDF-1α/PDGF-B pathway is required for differentiation of PDGFR-β+ bone marrow cells into mature pericytes. |
In vitro SDF-1α stimulation; 2-kb PDGF-B promoter reporter assay; chromatin immunoprecipitation (ChIP) for ELK-1; in vivo tumor model; pericyte differentiation assay |
Molecular cancer research : MCR |
High |
21911740
|
| 2013 |
Venous malformation-causing TIE2 mutations (L914F) cause AKT-dependent chronic suppression of PDGFB production in endothelial cells; mutant TIE2 L914F chronically activates AKT in a ligand-independent manner, reducing PDGFB secretion and thereby impairing mural cell recruitment, contributing to abnormal vascular channel formation. |
Global gene expression profiling of TIE2-mutant ECs; in vitro TIE2 L914F and R849W expression; AKT inhibitor treatment; ex vivo patient tissue PDGFB measurement |
Human molecular genetics |
High |
23633549
|
| 2013 |
Mutations in PDGFB cause autosomal dominant idiopathic basal ganglia calcification (IBGC) in humans; in mice, loss of endothelial PDGFB leads to pericyte deficiency and blood-brain barrier dysfunction, and hypomorphic Pdgfb alleles develop age-related brain calcifications that correlate with degree of pericyte and BBB deficiency. |
Human genetic analysis; mouse hypomorphic Pdgfb alleles; histological and radiological brain calcification assessment; pericyte quantification; BBB permeability assay |
Nature genetics |
High |
23913003
|
| 2013 |
LHX2 transcription factor directly induces PDGF-B expression in tumor cells, driving autocrine PDGFRβ signaling for cell migration/invasion and paracrine signaling to pericytes for vessel maturation and primary tumor growth; pharmacological inhibition of PDGF-B/PDGFRβ signaling reduces vessel functionality, tumor growth, and LHX2-induced invasion. |
Loss/gain-of-function in transgenic mouse models; pharmacological PDGFB/PDGFRβ inhibition; in vitro migration/invasion assays; vessel maturation analysis |
Molecular oncology |
High |
24423492
|
| 2015 |
Germline PDGFB mutations causing Primary Familial Brain Calcification (PFBC) lead to complete loss of PDGF-B function through abolished protein synthesis or defective PDGF-Rβ binding/stimulation; the Pdgfbret/ret mouse model (lacking the proteoglycan-binding retention motif) develops brain calcification, demonstrating that altered tissue distribution of PDGF-B protein is sufficient to cause calcification. |
In vitro functional analysis of six PDGFB mutations; PDGF-Rβ binding assay; autophosphorylation assay; heterozygous knockout mice; Pdgfbret/ret mice; brain calcification assessment; pericyte coverage quantification; BBB analysis |
PloS one |
High |
26599395
|
| 2016 |
Transgenic cardiac overexpression of PDGF-B induces focal fibrosis and moderate cardiac hypertrophy, mediated primarily via PDGFRβ; the weaker fibrotic effect of PDGFB (compared to PDGF-A, which is more potent via PDGFRα) reflects differences in receptor affinity, implicating PDGFRα in interstitial mesenchymal cells as the main mediator of strong cardiac fibrosis. |
Alpha-myosin heavy chain promoter-driven transgenic overexpression; histological and cardiac size analysis; immunohistochemistry for PDGF receptors |
Experimental cell research |
Medium |
27816607
|
| 2017 |
PDGFB expressed by lymphatic endothelial cells (LECs) of collecting vessels is required for smooth muscle cell (SMC) recruitment to lymphatic vessels; LEC-specific Pdgfb deletion prevents SMC recruitment causing vessel dilation and failure of pulsatile contraction; extracellular matrix retention of PDGFB is required for SMC recruitment, and low ECM-binding components around capillaries provide a checkpoint preventing inappropriate SMC investment of capillaries. |
LEC-specific Cre-mediated Pdgfb deletion; PDGFB overexpression in LECs; histological analysis; ECM retention assay; pulsatile contraction measurement |
Development (Cambridge, England) |
High |
28851707
|
| 2020 |
Platelet-specific conditional knockout of PDGFB impairs tumor vascular pericyte coverage and function, leading to enhanced hypoxia, epithelial-to-mesenchymal transition, elevated circulating tumor cells, and increased spontaneous metastasis, establishing a novel role for platelet-derived PDGFB in maintaining tumor vascular integrity. |
Platelet-specific Cre-mediated Pdgfb conditional knockout; two tumor mouse models; pericyte coverage quantification; hypoxia markers; EMT markers; circulating tumor cell counting; metastasis quantification |
Cancer research |
High |
32586981
|
| 2020 |
Endothelial Twist1 transcription factor mediates hypoxia-induced PDGFB upregulation; Twist1 overexpression increases PDGFB expression in pulmonary arterial endothelial cells; knockdown of endothelial Twist1 suppresses hypoxia-induced αSMA-positive cell accumulation and PDGFB upregulation in an in vivo gel implant model; Twist1 and PDGFB levels are elevated in IPAH patient pulmonary artery endothelial cells. |
Twist1 overexpression/knockdown; in vivo hydrogel implant model on mouse lung; immunofluorescence; IPAH patient cell analysis |
Scientific reports |
High |
32371931
|
| 2021 |
Adult-induced endothelial deletion of Pdgfb in 2-month-old mice causes slowly progressive pericyte loss (reaching ~50% decrease in endothelial:pericyte ratio and >70% decrease in pericyte marker expression by 12–18 months) and increased BBB permeability; in contrast to constitutive Pdgfb loss, adult-induced loss does not cause vessel dilation, arterio-venous skewing, or microvascular calcification, distinguishing developmental from maintenance roles of PDGFB. |
Tamoxifen-inducible endothelial-specific Cre; longitudinal pericyte quantification; BBB permeability assay; vessel morphology analysis |
Journal of cerebral blood flow and metabolism |
High |
34689641
|
| 2021 |
Macrophage-derived PDGF-B is critical for pathological smooth muscle cell expansion (distal muscularization) in pulmonary hypertension; macrophage-specific deletion of Pdgfb (LysM-Cre) prevents hypoxia-induced distal muscularization and PH; PDGF-B is upregulated in macrophages from human PAH patients; nanoparticle-mediated siRNA knockdown of Pdgfb specifically in lung macrophages prevents hypoxia-induced PH and right ventricular hypertrophy. |
LysM-Cre conditional Pdgfb knockout; clodronate macrophage depletion; HIF-1α and HIF-2α conditional knockouts; macrophage-conditioned medium SMC proliferation/migration assay; nanoparticle siRNA delivery; human PAH patient macrophage analysis |
JCI insight |
High |
33591958
|
| 2021 |
C/EBPβ transcription factor directly binds PDGFB promoter elements to facilitate PDGFB transcription in anoikis-resistant gastric cancer cells; secreted PDGFB promotes cancer cell survival via a C/EBPβ-dependent self-feedback loop and promotes angiogenesis via MAPK/ERK signaling in vascular endothelial cells. |
ChIP showing direct C/EBPβ binding to PDGFB promoter; loss/gain-of-function experiments; MAPK/ERK signaling analysis; in vitro and in vivo metastasis models |
Oncogene |
High |
34341514
|
| 2022 |
Microglia constitutively release PDGFB, which signals via PDGFRα on hypothalamic paraventricular nucleus neurons to promote Kv4.3 (potassium channel) expression; ablation of microglia, conditional deletion of microglial PDGFB, or suppression of neuronal PDGFRα elevates pre-sympathetic neuronal excitability and sympathetic outflow, causing hypertension; central supplementation of exogenous PDGFB suppresses the pressor response. |
Microglial ablation; conditional microglial Pdgfb deletion; neuronal PDGFRα suppression; electrophysiology; sympathetic outflow measurement; blood pressure monitoring; exogenous PDGFB central administration |
Immunity |
High |
35863346
|
| 2023 |
In adult mice, microglia are the primary source of PDGFB in the CNS (transitioning from endothelial cells in neonates); acute loss of microglial PDGFB profoundly impairs BBB integrity in adults, causing lethal microhemorrhages upon endotoxin challenge; acute loss of endothelial PDGFB has minimal effects on adult BBB but severely impairs neonatal CNS vasculature. |
Transcriptomic analysis; in situ hybridization; acute conditional cell-specific Pdgfb deletion in adult vs. neonatal mice; BBB permeability assay; endotoxin challenge survival model |
Brain, behavior, and immunity |
High |
37992789
|
| 2023 |
PROX1 transcription factor inhibits PDGFB expression in valvular endothelial cells (VECs) partially via FOXC2; conditional deletion of Prox1 from VECs upregulates PDGFB, leading to progressive myxomatous valve degeneration; conditional overexpression of PDGFB in VECs recapitulates the Prox1-knockout phenotype; pharmacological inhibition of PDGFB signaling with imatinib partially ameliorates valve defects. |
Conditional Prox1 VEC-specific knockout; conditional PDGFB overexpression in VECs; conditional FOXC2 knockdown; echocardiography; histology; electron microscopy; imatinib pharmacological rescue; human mitral valve prolapse sample analysis |
Circulation research |
High |
37555328
|