Studied on physiological functions of Gas6 and development of its inhibitors
| Project/Area Number |
12558079
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Functional biochemistry
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| Research Institution | Tohoku University |
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Principal Investigator |
MIZUNO Kensaku Tohoku University, Graduate Schoofof Life Sciences, Professor, 大学院・生命科学研究科, 教授 (70128396)
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| Co-Investigator(Kenkyū-buntansha) |
NAKANO Toru Shionogi & Co., Ltd., Discovery Research Laboratories, Managing Researcher, 創薬研究科, 主管研究員
ARAI Hidenori Kyoto University, Department of Geriatric Medicine, Assistant Professor, 大学院・医学研究科, 助手 (60232021)
OHASHI Kazumasa Tohoku University, Graduate Schoofof Life Sciences, Associate Professor, 大学院・生命科学研究科, 助教授 (10312539)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥13,600,000 (Direct Cost: ¥13,600,000)
Fiscal Year 2001: ¥5,800,000 (Direct Cost: ¥5,800,000)
Fiscal Year 2000: ¥7,800,000 (Direct Cost: ¥7,800,000)
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| Keywords | Gas6 / growth factor / apoptosis / mesangial cell / glomerulonephritis / Axl / STAT3 / 腎メサンジウム細胞 / ワルファリン |
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| Research Abstract |
The product of growth arrest-specific gene 6 (Gas6) is a ligand for receptor tyrbsjne kinases, Axl, Sky, and Mer. We showed that Gas6 specifically binds to phosphatidylserine through the N-terminal Gla domain. We found that Gas6 enhanced the uptake of phosphatidylserine liposomes and apoptotic cells by macrophages. These results suggest that Gas6 help phagocytic cells recognize cells with phosphatidylserine exposed on their cell surfaces and may play a role in the clearance of apoptotic cells. Gas6 stimulates mesangial cell proliferation through stimulation of its cell-surface receptor Axl. We showed that warfarin and the extracellular domain of Axl inhibit mesangial cell proliferation by interfering the Gas6/Axl pathway in vitro. In an experimental model of mesangial proliferative glomerulonephritis induced by anti Thy1 antibody, expression of Qas6 and Axl was increased in glomeruli. Administration of warfarin or Axl-Fc inhibited mesangial cell proliferation. These results suggest that Gas6/Axl pathway plays a key role in mesangial cell proliferation in vivo, and could be a potentially important therapeutic target for the treatment of renal disease. We also found that STAT3 is phosphorylated and activated by Gas6 stimulation and plays a key role in the signaling pathway in Gas6-mediated mesangial cell proliferation in vitro and in vivo.
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Report
(3 results)
Research Products
(15 results)
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[Publications] Yanagita, M., Arai, H., Ishii, K., Nakano, T., Ohashi, K., Mizuno, K., Varnum, B., Fukatsu A., Doi T. and Kita, T.: "Gas6 regulates mesangial cell proliferation through Axl in experimental glomerulonephritis."Am. J. Pathol.. 158. 1423-1432 (2001)
Description
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Related Report
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[Publications] Yanagita, M., Arai, H., Nakano T., Ohashi, K., _ Mizuno, K., Fukatsu, A., Doi, T., and Kita, T.: "Gas6 induces mesangial cell proliferation via latent transcription factor STAT3."J. Biol. Chem.. 276. 42364-42369 (2001)
Description
「研究成果報告書概要(欧文)」より
Related Report
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