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Gene Review

Pdgfb  -  platelet derived growth factor, B polypeptide

Mus musculus

Synonyms: PDGF subunit B, PDGF-2, PDGF-B, Platelet-derived growth factor B chain, Platelet-derived growth factor beta polypeptide, ...
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Disease relevance of Pdgfb


High impact information on Pdgfb


Chemical compound and disease context of Pdgfb

  • These results indicated that PDGF-B overexpression can stimulate increased collagen deposition and vascular smooth muscle hyperplasia following asbestos inhalation and that a limited exposure (8 times) to chrysotile aerosol can produce long-lasting fibrotic lesions [11].
  • In the present study we examined potential causes of this phenotypic variation and tested whether constitutive PDGF-B expression exacerbated fibrosis induced by bleomycin and silica [12].

Biological context of Pdgfb


Anatomical context of Pdgfb

  • However, in marked contrast to the embryonic lethality of Pdgfb null mutants, the endothelium-specific mutants survived into adulthood with persistent pathological changes, including brain microhemorrhages, focal astrogliosis, and kidney glomerulus abnormalities [1].
  • Here we demonstrate that transcription from a promoter containing NF-kappaB binding sequences as well as the DNA binding activity of NF-kappaB were increased in PDGF-B-chain-transformed mouse fibroblast cells [18].
  • However, the PDGF-B gene in the NPA cells was hypomethylated compared to that in normal thyroid tissue or WRO cells [15].
  • PDGF-B released from colon tumor cells regulated tumor growth in athymic mice in a paracrine manner by inducing blood vessel formation [16].
  • TGF beta 1 was capable of inducing PDGF-B expression in the undifferentiated U9 colon carcinoma cell line, but this sensitivity was not seen in differentiated cells [16].

Associations of Pdgfb with chemical compounds


Physical interactions of Pdgfb

  • Furthermore, the stimulatory effects of TGF beta 1 on c-sis mRNA expression were shown to be pertussis-toxin sensitive and could be mimicked by direct activation of G-proteins with AIF4-. These results demonstrate that in AKR-2B cells a pertussis-toxin-sensitive guanine nucleotide regulatory protein(s) is coupled to TGF beta 1 receptor binding [22].
  • Analysis of tyrosine-phosphorylated proteins demonstrated that Crk-associated substrate (p130(Cas)), not the activated PDGFbetaR itself, is the major Nck SH2 domain-binding protein in PDGF-B-stimulated cells [23].
  • A 250-bp PDGF-B gene promoter attached to a reporter gene was shown to reproduce this TPA-induced activation [24].

Co-localisations of Pdgfb


Regulatory relationships of Pdgfb

  • PDGF-B overexpression causes liver fibrosis without significantly upregulating TGF-beta1, suggesting a TGF-beta-independent mechanism [2].
  • Membrane-anchored form of v-sis/PDGF-B induces mitogenesis without detectable PDGF receptor autophosphorylation [25].
  • Expression of an ATP binding mutant of PKC-delta inhibits Sis-induced transformation of NIH3T3 cells [26].
  • Functional studies confirmed the senescent dysregulation of TNF-alpha receptor pathways, demonstrating that TNF-alpha induced PDGF-B expression in cardiac microvascular endothelial cells of 4-mo-old, but not 24-mo-old, rats [27].
  • Consistent with these in vitro findings, MT1-MMP-deficient brain tissues display a marked reduction in mural cell density as well as abnormal vessel wall morphology similar to that reported in mice expressing PDGF-B or PDGFRbeta hypomorphic alleles [28].

Other interactions of Pdgfb


Analytical, diagnostic and therapeutic context of Pdgfb


  1. Endothelium-specific ablation of PDGFB leads to pericyte loss and glomerular, cardiac and placental abnormalities. Bjarnegård, M., Enge, M., Norlin, J., Gustafsdottir, S., Fredriksson, S., Abramsson, A., Takemoto, M., Gustafsson, E., Fässler, R., Betsholtz, C. Development (2004) [Pubmed]
  2. Liver fibrosis induced by hepatic overexpression of PDGF-B in transgenic mice. Czochra, P., Klopcic, B., Meyer, E., Herkel, J., Garcia-Lazaro, J.F., Thieringer, F., Schirmacher, P., Biesterfeld, S., Galle, P.R., Lohse, A.W., Kanzler, S. J. Hepatol. (2006) [Pubmed]
  3. Localization of the murine activating transcription factor 4 gene to mouse chromosome 15. Mielnicki, L.M., Elliott, R.W., Pruitt, S.C. Genomics (1993) [Pubmed]
  4. Mice deficient for PDGF B show renal, cardiovascular, and hematological abnormalities. Levéen, P., Pekny, M., Gebre-Medhin, S., Swolin, B., Larsson, E., Betsholtz, C. Genes Dev. (1994) [Pubmed]
  5. Endothelial PDGF-B retention is required for proper investment of pericytes in the microvessel wall. Lindblom, P., Gerhardt, H., Liebner, S., Abramsson, A., Enge, M., Hellstrom, M., Backstrom, G., Fredriksson, S., Landegren, U., Nystrom, H.C., Bergstrom, G., Dejana, E., Ostman, A., Lindahl, P., Betsholtz, C. Genes Dev. (2003) [Pubmed]
  6. Chimaeric analysis reveals role of Pdgf receptors in all muscle lineages. Crosby, J.R., Seifert, R.A., Soriano, P., Bowen-Pope, D.F. Nat. Genet. (1998) [Pubmed]
  7. PDGF-A signaling is a critical event in lung alveolar myofibroblast development and alveogenesis. Boström, H., Willetts, K., Pekny, M., Levéen, P., Lindahl, P., Hedstrand, H., Pekna, M., Hellström, M., Gebre-Medhin, S., Schalling, M., Nilsson, M., Kurland, S., Törnell, J., Heath, J.K., Betsholtz, C. Cell (1996) [Pubmed]
  8. Transformation of NIH 3T3 cells by a human c-sis cDNA clone. Clarke, M.F., Westin, E., Schmidt, D., Josephs, S.F., Ratner, L., Wong-Staal, F., Gallo, R.C., Reitz, M.S. Nature (1984) [Pubmed]
  9. Pericyte loss and microaneurysm formation in PDGF-B-deficient mice. Lindahl, P., Johansson, B.R., Levéen, P., Betsholtz, C. Science (1997) [Pubmed]
  10. Comparison of biological properties and transforming potential of human PDGF-A and PDGF-B chains. Beckmann, M.P., Betsholtz, C., Heldin, C.H., Westermark, B., Di Marco, E., Di Fiore, P.P., Robbins, K.C., Aaronson, S.A. Science (1988) [Pubmed]
  11. Effect of platelet-derived growth factor on the development and persistence of asbestos-induced fibroproliferative lung disease. Li, J., Poovey, H.G., Rodriguez, J.F., Brody, A., Hoyle, G.W. J. Environ. Pathol. Toxicol. Oncol. (2004) [Pubmed]
  12. Lung pathology in platelet-derived growth factor transgenic mice: effects of genetic background and fibrogenic agents. Li, J., Ortiz, L.A., Hoyle, G.W. Exp. Lung Res. (2002) [Pubmed]
  13. The IL-2 receptor beta chain gene (Il-2rb) is closely linked to the Pdgfb locus on mouse chromosome 15. Malek, T.R., Vincek, V., Gatalica, B., Bucan, M. Immunogenetics (1993) [Pubmed]
  14. Platelet-derived growth factor (PDGF) receptor-alpha activates c-Jun NH2-terminal kinase-1 and antagonizes PDGF receptor-beta -induced phenotypic transformation. Yu, J., Deuel, T.F., Kim, H.R. J. Biol. Chem. (2000) [Pubmed]
  15. Growth factor production by human thyroid carcinoma cells: abundant expression of a platelet-derived growth factor-B-like protein by a human papillary carcinoma cell line. Matsuo, K., Tang, S.H., Sharifi, B., Rubin, S.A., Schreck, R., Fagin, J.A. J. Clin. Endocrinol. Metab. (1993) [Pubmed]
  16. Platelet-derived growth factor-B increases colon cancer cell growth in vivo by a paracrine effect. Hsu, S., Huang, F., Friedman, E. J. Cell. Physiol. (1995) [Pubmed]
  17. Genetic mapping of the mouse proto-oncogene c-sis to chromosome 15. Kozak, C.A., Sears, J.F., Hoggan, M.D. Science (1983) [Pubmed]
  18. Activation of NF-kappaB is required for PDGF-B chain to transform NIH3T3 cells. Shimamura, T., Hsu, T.C., Colburn, N.H., Bejcek, B.E. Exp. Cell Res. (2002) [Pubmed]
  19. Smooth muscle cell immediate-early gene and growth factor activation follows vascular injury. A putative in vivo mechanism for autocrine growth. Miano, J.M., Vlasic, N., Tota, R.R., Stemerman, M.B. Arterioscler. Thromb. (1993) [Pubmed]
  20. Dominant-negative mutants of a platelet-derived growth factor gene. Mercola, M., Deininger, P.L., Shamah, S.M., Porter, J., Wang, C.Y., Stiles, C.D. Genes Dev. (1990) [Pubmed]
  21. The oncogene PDGF-B provides a key switch from cell death to survival induced by TNF. Au, P.Y., Martin, N., Chau, H., Moemeni, B., Chia, M., Liu, F.F., Minden, M., Yeh, W.C. Oncogene (2005) [Pubmed]
  22. Transforming growth factor beta 1 treatment of AKR-2B cells is coupled through a pertussis-toxin-sensitive G-protein(s). Howe, P.H., Leof, E.B. Biochem. J. (1989) [Pubmed]
  23. Requirement of Nck adaptors for actin dynamics and cell migration stimulated by platelet-derived growth factor B. Rivera, G.M., Antoku, S., Gelkop, S., Shin, N.Y., Hanks, S.K., Pawson, T., Mayer, B.J. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  24. Identification and characterization of an essential, activating regulatory element of the human SIS/PDGFB promoter in human megakaryocytes. Jin, H.M., Brady, M.L., Fahl, W.E. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  25. Membrane-anchored form of v-sis/PDGF-B induces mitogenesis without detectable PDGF receptor autophosphorylation. Lee, B.A., Donoghue, D.J. J. Cell Biol. (1991) [Pubmed]
  26. Expression of an ATP binding mutant of PKC-delta inhibits Sis-induced transformation of NIH3T3 cells. Li, W., Michieli, P., Alimandi, M., Lorenzi, M.V., Wu, Y., Wang, L.H., Heidaran, M.A., Pierce, J.H. Oncogene (1996) [Pubmed]
  27. Age-associated impairment in TNF-alpha cardioprotection from myocardial infarction. Cai, D., Xaymardan, M., Holm, J.M., Zheng, J., Kizer, J.R., Edelberg, J.M. Am. J. Physiol. Heart Circ. Physiol. (2003) [Pubmed]
  28. An MT1-MMP-PDGF receptor-beta axis regulates mural cell investment of the microvasculature. Lehti, K., Allen, E., Birkedal-Hansen, H., Holmbeck, K., Miyake, Y., Chun, T.H., Weiss, S.J. Genes Dev. (2005) [Pubmed]
  29. Cellular DNA region involved in induction of thymic lymphomas (Mlvi-2) maps to mouse chromosome 15. Tsichlis, P.N., Strauss, P.G., Kozak, C.A. Mol. Cell. Biol. (1984) [Pubmed]
  30. Assignment of the Ly-6--Ril-1--Sis--H-30--Pol-5/Xmmv-72--Ins-3--Krt-1--Int-1 --Gdc-1 region to mouse chromosome 15. Meruelo, D., Rossomando, A., Scandalis, S., D'Eustachio, P., Fournier, R.E., Roop, D.R., Saxe, D., Blatt, C., Nesbitt, M.N. Immunogenetics (1987) [Pubmed]
  31. Genetic analysis of alcohol intake in recombinant inbred and congenic strains derived from A/J and C57BL/6J progenitors. Gill, K., Boyle, A.E. Mamm. Genome (2005) [Pubmed]
  32. Photoreceptor-specific expression of platelet-derived growth factor-B results in traction retinal detachment. Seo, M.S., Okamoto, N., Vinores, M.A., Vinores, S.A., Hackett, S.F., Yamada, H., Yamada, E., Derevjanik, N.L., LaRochelle, W., Zack, D.J., Campochiaro, P.A. Am. J. Pathol. (2000) [Pubmed]
  33. Microarray analysis of blood microvessels from PDGF-B and PDGF-Rbeta mutant mice identifies novel markers for brain pericytes. Bondjers, C., He, L., Takemoto, M., Norlin, J., Asker, N., Hellström, M., Lindahl, P., Betsholtz, C. FASEB J. (2006) [Pubmed]
  34. Transcription profiling of platelet-derived growth factor-B-deficient mouse embryos identifies RGS5 as a novel marker for pericytes and vascular smooth muscle cells. Bondjers, C., Kalén, M., Hellström, M., Scheidl, S.J., Abramsson, A., Renner, O., Lindahl, P., Cho, H., Kehrl, J., Betsholtz, C. Am. J. Pathol. (2003) [Pubmed]
  35. Five PDGF B amino acid substitutions convert PDGF A to a PDGF B-like transforming molecule. LaRochelle, W.J., Pierce, J.H., May-Siroff, M., Giese, N., Aaronson, S.A. J. Biol. Chem. (1992) [Pubmed]
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