| Project/Area Number |
11670727
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | University of Occupational and Environmental Health |
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Principal Investigator |
NAKASHIMA Yasuhide UOEH, School of Medicine, Professor, 医学部, 教授 (20038780)
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| Co-Investigator(Kenkyū-buntansha) |
TANAKA Hiroshi UOEH, School of Medicine, Assistant Professor, 医学部, 講師 (30269055)
OKAZAKI Masahiro UOEH, School of Medicine, Assistant Professor, 医学部, 講師 (40233316)
TASAKI Hiromi UOEH, School of Medicine, Associate Professor, 医学部, 助教授 (60216950)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2000: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1999: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | Profilin / Profilin receptor / Immunoelectron microscopy / Intracellular signal transduction / bFGF / AP-1 / Glomerulonephritis / Mesangium / ラット / thy-1腎炎 / 糸球体 / レセプター |
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| Research Abstract |
Profilin is known to bind to actin monomers to regulate actin polymerization, and to phosphatidylinositol 4,5-bisphosphate to inhibit hydrolysis by unphosphorylated phospholipase C-γ1. We recently reported that profilin is overexpressed in glomerular mesangial cells of anti-Thy-1.1 glomerulonephritis rats and is accumulated in the extracellular space around mesangial cells. In the present study, we examined the biological activities of extracellular profilin. Scatchard analysis indicated the existence of a single class of cell surface binding site with similar K_ds for purified splenic and recombinant profilin in cultured rat mesangial cells. Profilin increased [^3H]thymidine incorporation in a dose-dependent manner and had additive effects on PDGF-induced [^3H]thymidine incorporation. Profilin increased AP-1 DNA binding activity in a concentration- (ED_<50> = 30 nM) and time-dependent manner followed the transient gene expression of c-jun measured by gel shift assay and competitive reverse transcribed-PCR.Pretreatment of profilin with anti-profilin inhibitory antibody suppressed profilin-induced AP-1 activation and [^3H]thymidine incorporation. Furthermore, profilin induced a rapid and transient activation of protein kinase C, and staurosporine and H-7 diminished profilin-induced activation of AP-1, suggesting protein kinase C-dependent activation of AP-1. These findings indicate that profilin in the extracellular space can bind to cell surface receptors of mesangial cells and act as an inducer of signal transduction. These results suggest that extracellular profilin may be involved in the progression of glomerular diseases by affecting cell growth.
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