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Gene Review

Pdgfa  -  platelet-derived growth factor alpha...

Rattus norvegicus

Synonyms: PDGF subunit A, PDGF-1, Platelet-derived growth factor A chain, Platelet-derived growth factor alpha polypeptide, Platelet-derived growth factor subunit A, ...
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Disease relevance of Pdgfa

  • Moreover, transfection of tetanus toxin light chain, which cleaves the v-SNAREs VAMP2 and VAMP3, reduced insulin-induced GLUT4myc translocation by >70% but did not affect the PDGF response [1].
  • We wanted to determine the effect of egr-1 antisense oligonucleotide on cysteamine-induced duodenal ulcers as well as on the expression of bFGF, PDGF, and VEGF, of which synthesis is modulated by Egr-1 [2].
  • To examine the possible involvement of platelet-derived growth factor (PDGF) in the pulmonary vascular remodeling caused by hypoxia, we cloned rat PDGF A- and B-chain cDNA and prepared specific cRNA probes [3].
  • Increased expression of PDGF A- and B-chain genes in rat lungs with hypoxic pulmonary hypertension [3].
  • Pertussis toxin (250 ng/ml) had no effect on PDGF-induced channel activity (P = 0.45, n = 6) [4].

Psychiatry related information on Pdgfa

  • The expression of platelet-derived growth factor (PDGF) was studied in a rat model of Huntington's disease, produced by unilateral intrastriatal ibotenic acid injections [5].
  • PDGF increased [Ca2+]f from 78 +/- 12 to 192 +/- 22 nM, but the time response was different from that seen with PAF [6].

High impact information on Pdgfa

  • PDGF is a potent mitogen for O-2A progenitor cells in vitro [7].
  • We propose that astrocyte-derived PDGF is crucial for the control of myelination in the developing central nervous system [7].
  • SSV-transformed cells have reduced numbers of high-affinity 125I-PDGF receptors; PDGF/p28v-sis receptor was purified from SSV-NIH 3T3 cells and retained active protein tyrosine kinase activity stimulated by PDGF [8].
  • Secreted p28v-sis appears to stimulate autocrine cell growth of SSV-transformed cells because anti-PDGF antisera block 3H-thymidine incorporation into growing SSV-NIH 3T3 and SSV-NRK cells [8].
  • Simian sarcoma virus-transformed NIH 3T3 (SSV-NIH 3T3) and SSV-NRK cells secrete a potent growth-promoting activity identical with the platelet-derived growth factor (PDGF) in mitogenic assays [8].

Chemical compound and disease context of Pdgfa

  • In mesangial cells, the intrinsic tyrosine kinase activity of the PDGF-beta receptor stimulates the formation of a membrane-bound growth factor receptor-binding protein 2/son of sevenless/PDGF-beta receptor complex and activation of the pertussis toxin-insensitive GTP-binding protein, p21-Ras, which leads to the opening of 1-pS Ca2+ channels [4].
  • To examine the role of PDGF in the development of diabetic nephropathy, we conducted immunohistochemical analysis for PDGF B-chain (PDGF-B) and PDGF beta-receptor (PDGFR-beta) in the glomeruli of streptozotocin-induced diabetic rats [9].
  • We speculate that the early pulmonary fibroblast hyperplasia observed following exposure to 85% O2 is mediated by increased PDGF-B chain gene expression and may also be mediated by changes in PDGF B-type receptor gene expression [10].
  • However, Ang II causes cell hypertrophy, whereas PDGF causes hyperplasia [11].
  • In this study, we show that treatment with the selective PDGF receptor kinase inhibitor, STI571, formerly known as CGP57148B, decreased the interstitial hypertension and increased capillary-to-interstitium transport of 51Cr-EDTA in s.c. growing rat PROb colonic carcinomas [12].

Biological context of Pdgfa


Anatomical context of Pdgfa

  • These results reveal the S1P(1)-triggered, G(i)-Ras-ERK/p38 MAPK-KLF5-dependent, stimulatory regulation of PDGF gene transcription in vascular smooth muscle cells [17].
  • Insulin but not PDGF relies on actin remodeling and on VAMP2 for GLUT4 translocation in myoblasts [1].
  • These results suggest that insulin and PDGF rely differently on the actin cytoskeleton and on tetanus-toxin-sensitive VAMPs for mobilizing GLUT4 [1].
  • Cysteamine induced phosphorylation of ERK1/2 and enhanced the synthesis of bFGF, PDGF, and VEGF in the preulcerogenic stages of duodenal ulceration, whereas egr-1 antisense oligonucleotide markedly decreased the expression of these growth factors in the duodenal mucosa [2].
  • We investigated the signaling pathways mediating 1-pS Ca2+ channel activation by PDGF in cultured rat mesangial cells [4].

Associations of Pdgfa with chemical compounds

  • Latrunculin B, cytochalasin D and jasplakinolide, which disrupt actin dynamics, prevented insulin- and PDGF-induced actin remodeling but significantly inhibited GLUT4myc translocation only in response to insulin (75-85%, P<0.05), not to PDGF (20-30% inhibition) [1].
  • Consistent with these results, the PDGF-induced thymidine incorporation was increased in Rat1/NHERF2 cells, and the NHERF2-dependent increase of thymidine incorporation was prevented by treatment with LY294002 and PP2 but not with PD98059 [14].
  • Herein we investigated the effect of FK778 on acute rejection and on the expression of PDGF and TGF-beta both alone and in combination with cyclosporine (CsA) or tacrolimus (Tac) [18].
  • Tyrosine kinase inhibition (100 microM genistein or 10 microM tryphostin 9) abolished PDGF-induced channel activation (P < 0.02, n = 6) [4].
  • Nonfibrogenic carbonyl iron spheres induced similar changes in PDGF growth responses [19].

Physical interactions of Pdgfa


Regulatory relationships of Pdgfa


Other interactions of Pdgfa

  • In contrast, in the heart of the SHR and WKY rat, there was an age-related decrease in expression of both PDGF receptors and of the PDGF B chain [13].
  • A progressive increase with age in aortic steady-state messenger RNA (mRNA) levels of the receptor for the B chain of PDGF (PDGF-r beta) was present in all three strains but was greatest in the SHR [13].
  • Crosstalk between PDGF and IGF-I receptors in rat liver myofibroblasts: implication for liver fibrogenesis [26].
  • Platelet-derived growth factor (PDGF) and epidermal growth factor (EGF) are the potent mitogens for many cell types [15].
  • Both platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta) are major mitogens mediating mesenchymal cell proliferation and epithelial to mesenchymal cell transition [18].

Analytical, diagnostic and therapeutic context of Pdgfa

  • We therefore investigated by quantitative real time PCR (Taqman) the mRNA expression profiles of all four PDGF isoforms in transdifferentiating primary cultured hepatic stellate cells (HSC), an in vitro model system of hepatic fibrogenesis, either with or without stimulation of the cells with PDGF-BB or TGF-beta1 [16].
  • Northern blot analysis revealed that PDGF B-chain mRNA levels in the lungs were increased, reached a maximum of day 1, and were sustained at day 3, whereas PDGF A-chain mRNA levels reached a maximum on day 3 [3].
  • Western immunoblots revealed that PDGF-BB binding stimulates the formation of a membrane-bound complex consisting of growth factor receptor-binding protein 2, son of sevenless, and the PDGF-beta receptor [4].
  • CONCLUSIONS: Alloimmune injury induces the expression of PDGF ligands, especially of PDGF-AA, in the graft vasculature and sufficient immunosuppression with CsA suppresses the expression of PDGF and inhibits the development of CAV [27].
  • Immunoblotting indicated a true molecular size of 32 kDa for this PDGF-like growth factor [28].


  1. Insulin but not PDGF relies on actin remodeling and on VAMP2 for GLUT4 translocation in myoblasts. Török, D., Patel, N., Jebailey, L., Thong, F.S., Randhawa, V.K., Klip, A., Rudich, A. J. Cell. Sci. (2004) [Pubmed]
  2. Suppression of early growth response factor-1 with egr-1 antisense oligodeoxynucleotide aggravates experimental duodenal ulcers. Khomenko, T., Szabo, S., Deng, X., Jadus, M.R., Ishikawa, H., Osapay, K., Sandor, Z., Chen, L. Am. J. Physiol. Gastrointest. Liver Physiol. (2006) [Pubmed]
  3. Increased expression of PDGF A- and B-chain genes in rat lungs with hypoxic pulmonary hypertension. Katayose, D., Ohe, M., Yamauchi, K., Ogata, M., Shirato, K., Fujita, H., Shibahara, S., Takishima, T. Am. J. Physiol. (1993) [Pubmed]
  4. Ca2+ channel activation by platelet-derived growth factor-induced tyrosine phosphorylation and Ras guanine triphosphate-binding proteins in rat glomerular mesangial cells. Ma, H., Matsunaga, H., Li, B., Schieffer, B., Marrero, M.B., Ling, B.N. J. Clin. Invest. (1996) [Pubmed]
  5. Expression of platelet-derived growth factor after intrastriatal ibotenic acid injury. Sjöborg, M., Pietz, K., Ahgren, A., Yamada, N., Lindvall, O., Funa, K., Odin, P. Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale. (1998) [Pubmed]
  6. PAF and PDGF increase cytosolic [Ca2+] and phospholipase activity in mesangial cells. Bonventre, J.V., Weber, P.C., Gronich, J.H. Am. J. Physiol. (1988) [Pubmed]
  7. A role for platelet-derived growth factor in normal gliogenesis in the central nervous system. Richardson, W.D., Pringle, N., Mosley, M.J., Westermark, B., Dubois-Dalcq, M. Cell (1988) [Pubmed]
  8. Transforming protein of simian sarcoma virus stimulates autocrine growth of SSV-transformed cells through PDGF cell-surface receptors. Huang, J.S., Huang, S.S., Deuel, T.F. Cell (1984) [Pubmed]
  9. Immunohistochemical characterization of glomerular PDGF B-chain and PDGF beta-receptor expression in diabetic rats. Nakagawa, H., Sasahara, M., Haneda, M., Koya, D., Hazama, F., Kikkawa, R. Diabetes Res. Clin. Pract. (2000) [Pubmed]
  10. Platelet-derived growth factor and growth-related genes in rat lung. II. Effect of exposure to 85% O2. Han, R.N., Buch, S., Freeman, B.A., Post, M., Tanswell, A.K. Am. J. Physiol. (1992) [Pubmed]
  11. Angiotensin II stimulates MAP kinase kinase kinase activity in vascular smooth muscle cells, Role of Raf. Liao, D.F., Duff, J.L., Daum, G., Pelech, S.L., Berk, B.C. Circ. Res. (1996) [Pubmed]
  12. Inhibition of platelet-derived growth factor receptors reduces interstitial hypertension and increases transcapillary transport in tumors. Pietras, K., Ostman, A., Sjöquist, M., Buchdunger, E., Reed, R.K., Heldin, C.H., Rubin, K. Cancer Res. (2001) [Pubmed]
  13. Effects of hypertension and aging on platelet-derived growth factor and platelet-derived growth factor receptor expression in rat aorta and heart. Sarzani, R., Arnaldi, G., Takasaki, I., Brecher, P., Chobanian, A.V. Hypertension (1991) [Pubmed]
  14. NHERF2 increases platelet-derived growth factor-induced proliferation through PI-3-kinase/Akt-, ERK-, and Src family kinase-dependent pathway. Jung Kang, Y., Su Jeon, E., Jin Lee, H., Oh, Y.S., Suh, P.G., Sup Jung, J., Donowitz, M., Ho Kim, J. Cell. Signal. (2004) [Pubmed]
  15. The phyto-chemical (-)-epigallocatechin gallate suppresses gene expression of epidermal growth factor receptor in rat hepatic stellate cells in vitro by reducing the activity of Egr-1. Fu, Y., Chen, A. Biochem. Pharmacol. (2006) [Pubmed]
  16. Expression patterns of PDGF-A, -B, -C and -D and the PDGF-receptors alpha and beta in activated rat hepatic stellate cells (HSC). Breitkopf, K., Roeyen, C., Sawitza, I., Wickert, L., Floege, J., Gressner, A.M. Cytokine (2005) [Pubmed]
  17. Blood lipid mediator sphingosine 1-phosphate potently stimulates platelet-derived growth factor-A and -B chain expression through S1P1-Gi-Ras-MAPK-dependent induction of Kruppel-like factor 5. Usui, S., Sugimoto, N., Takuwa, N., Sakagami, S., Takata, S., Kaneko, S., Takuwa, Y. J. Biol. Chem. (2004) [Pubmed]
  18. The Effect of FK778 on Acute Rat Renal Allograft Rejection and Expression of Platelet-Derived Growth Factor and Transforming Growth Factor-Beta. Rintala, J.M., Savikko, J., Rintala, S.E., von Willebrand, E. Transplant. Proc. (2006) [Pubmed]
  19. Chrysotile asbestos upregulates gene expression and production of alpha-receptors for platelet-derived growth factor (PDGF-AA) on rat lung fibroblasts. Bonner, J.C., Goodell, A.L., Coin, P.G., Brody, A.R. J. Clin. Invest. (1993) [Pubmed]
  20. Angiotensin II induces transactivation of two different populations of the platelet-derived growth factor beta receptor. Key role for the p66 adaptor protein Shc. Heeneman, S., Haendeler, J., Saito, Y., Ishida, M., Berk, B.C. J. Biol. Chem. (2000) [Pubmed]
  21. NF1/X represses PDGF A-chain transcription by interacting with Sp1 and antagonizing Sp1 occupancy of the promoter. Rafty, L.A., Santiago, F.S., Khachigian, L.M. EMBO J. (2002) [Pubmed]
  22. Carvedilol inhibits platelet-derived growth factor-induced extracellular matrix synthesis by inhibiting cellular reactive oxygen species and mitogen-activated protein kinase activation. Park, J., Ha, H., Kim, M.S., Ahn, H.J., Huh, K.H., Kim, Y.S. J. Heart Lung Transplant. (2006) [Pubmed]
  23. Expression and developmental control of platelet-derived growth factor A-chain and B-chain/Sis genes in rat aortic smooth muscle cells. Majesky, M.W., Benditt, E.P., Schwartz, S.M. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  24. Induction of PDGF receptor-alpha in rat myofibroblasts during pulmonary fibrogenesis in vivo. Bonner, J.C., Lindroos, P.M., Rice, A.B., Moomaw, C.R., Morgan, D.L. Am. J. Physiol. (1998) [Pubmed]
  25. Effects of PDGF A-chain antisense oligodeoxynucleotides on growth of cardiovascular organs in stroke-prone spontaneously hypertensive rats. Kishioka, H., Fukuda, N., Wen-Yang, H., Nakayama, M., Watanabe, Y., Kanmatsuse, K. Am. J. Hypertens. (2001) [Pubmed]
  26. Crosstalk between PDGF and IGF-I receptors in rat liver myofibroblasts: implication for liver fibrogenesis. Novosyadlyy, R., Dudas, J., Pannem, R., Ramadori, G., Scharf, J.G. Lab. Invest. (2006) [Pubmed]
  27. Expression and localization of platelet-derived growth factor ligand and receptor protein during acute and chronic rejection of rat cardiac allografts. Lemström, K.B., Koskinen, P.K. Circulation (1997) [Pubmed]
  28. Neuroblastoma cells express c-sis and produce a transforming growth factor antigenically related to the platelet-derived growth factor. van Zoelen, E.J., van de Ven, W.J., Franssen, H.J., van Oostwaard, T.M., van der Saag, P.T., Heldin, C.H., de Laat, S.W. Mol. Cell. Biol. (1985) [Pubmed]
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