Gene expression of platelet-derived growth factor (PDGF) and PDGF receptor in glomerulonephritis

• Project/Area Number: 02670277
• Research Category: Grant-in-Aid for General Scientific Research (C)
• Allocation Type: Single-year Grants
• Research Field: 内科学一般
• Research Institution: Toyama Medical and Pharmaceutical University
• Principal Investigator: IIDA Hiroyuki Toyama Medical & Pharmaceutical University Faculty of Medicine, Associate Professor, 医学部, 助教授 (50126504)
• Co-Investigator(Kenkyū-buntansha): TAKATA Masanobu Toyama Medical & Pharmacutical University Hospital, Assistant Professor, 附属病院, 講師 (00115180)
• Project Period (FY): 1990 – 1991
• Project Status: Completed (Fiscal Year 1991)
• Budget Amount: ¥2,300,000 (Direct Cost: ¥2,300,000); Fiscal Year 1991: ¥700,000 (Direct Cost: ¥700,000); Fiscal Year 1990: ¥1,600,000 (Direct Cost: ¥1,600,000)
• Keywords: Glomerulonephritis / Platelet-derived growth factor (PDGF) / PDGF receptor / mesangial cell proliferation / Crescentic glomerulonephritis / lupus nephritis / Gene expression / Northern blot / ノ-ザンブロッティング / 半月体形成性糸球体腎炎 / 1prマウス / 遺伝子発現 / 免疫組織化学 / 増殖性腎炎 / メサンギウム細胞増殖

Research Abstract

We investigated whether gene expression of platelet-derived growth factor (PDGF), or its receptor (PDGF-R) was upregulated in a rat model of mesangial proliferative glomerulonephritis induced with a single intravenous injection of anti-thymocyte serum. A marked increase in both PDGF B-chain and PDGF-R beta-Subunit was demonstrated in glomerular RNA by Northern blot analysis 3 and 5 days after disease induction, corresponding to the time of mesangial cell proliferation. Both complement depletion and platelet depletion significantly reduced glomerular cell proliferation and gene expression of PDGF and PDGF-R. Thus, it is suggested that the upregulation of PDGF and PDGF-R expression may play an important role in the pathogenesis of mesangial proliferative glomerulonephritis.
We also investigated the localization of PDGF B-chain in the glomeruli of murine lupus nephritis. Immunohistochemistry revealed PDGF B-chain in Glomeruli and crescents from MRL/l mice at 20 weeks of age, corresponding to the time of glomerular cell proliferation and crescent formation. These results suggest that PDGF B-chain plays an important role in the pathogenesis of lupus nephritis.

Research Products

• [Publications] Fujita Masuo: "Effect of the immunosuppressive agent,ciclosporin on experimental immune complex glomerulonephritis in rats" Nephron. 57. 201-205 (1991)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Richard J.Johnson: "Platelet-complement interactions in mesangial proliferative nephritis in the rat" American Journal of Pathology. 138. 313-321 (1991)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Iida Hiroyuki: "Platelet-derived growth factor (PDGF) and PDGF receptor (PDGF) expression are upregulated in mesangial proliferative nephritis:An effect mediated by complement and platelets" Acta Medica Biol. 39(suppl). 103-104 (1991)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Iida Hiroyuki: "Platelet-derived growth factor (PDGF) and PDGF receptor are induced in mesangial proliferative nephritis in the rat" Proceedings of National Academyof Science (U.S.A). 88. 6560-6564 (1991)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Iida Hiroyuki: "Effects of the platelet-activating factor antagonists CV-6209 and CV-3988 on nephrotoxic serum nephritis in the rat" Nephron. (1992)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Iida Hiroyuki: "Glomerulosclerosis in the rat induced by repeated immune-mediated mesangial cell injury" Am J Kidney Dis.
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] 飯田 博行: "Annual Review腎蔵1992(分担)" 中外医学社、東京, 8 (1992)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Iida H, Johnson RJ: "Platelet-derived growth factor (PDGF) and PDGF-receptor gene expression are upregulated in mesangial proliferative nephritis : An effect mediated by complement and platelets." Acta Medica Biol. 39(suppl). 103-104 (1991)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Iida H, Seifert R, Alpers CE, Gronwald RGK, Phillips PE, Pritzl P, Gordon K, Gown AM, Ross R, Bowen-Pope DF, Johnson JR: "Platelet-derived growth factor (PDGF) and PDGF receptor are induced in mesangial proliferative nephritis in the rat." Prco Natl Acad Sci USA. 88. 6560-6564 (1991)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Fujita M, Iida H, Asaka M, Izumino K, Takata M, Sasayama S: "Effect of the immunosuppressive agent, cyclosporine on experimental immune complex glomerulonephritis in rats." Nephron. 57. 201-205 (1991)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Iida H, Fujita M, Izumno K, Asaka M, Entani C, Tak Takata M, Sasayama S: "Effects of the platelet-activating factor antagonists CV-6209 and CA-3988 on nephrotoxic serum nephritis in the rat." Nephron. (1992)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Iida Hiroyuki: "Effects of the plateletーactivating factor antagonists CVー6209 and CVー3988 on nephrotoxic serum nephritis in the rat" Nephron. (1992)
• [Publications] Iida Hiroyuki: "Glomerulosclerosis in the rat induced by repeated immuneーmediated mesangial cell injury" Am J Kidney Dis.
• [Publications] 飯田 博行: "Annual Review腎臓1992(分担)" 中外医学社、東京, (1992)
• [Publications] Fujita Masuo: "Effect of the immunosuppressive agent,ciclosporin on experimental immune complex glomerulonephritis in rats." Nephron. 57. 201-205 (1991)
• [Publications] Richard J.Johnson: "Plateletーcomplement interactions in mesangial proliferative nephritis in the rat." American Journal Pathology. 138. 313-321 (1991)
• [Publications] Iida Hiroyuki: "Plateletーderived growth factor(PDGF)and PDGF receptor(PDGFーR)expression in mesangial proliferative nephritis(MesPGN)" Journal of the American Society of Nephrology. 1. 526 (1990)
• [Publications] Iida Hiroyuki: "Plateletーderived growth factor(PDGF)and PDGF receptor are induced in mesangial proliferative nephritis in the rat." Proceedings of National Academy of Science(U.S.A).