2002 Fiscal Year Final Research Report Summary
The Study of Progressive Factors to Developing Glomerular Injury
| Project/Area Number |
12470210
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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 | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | The University of Tokushima |
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Principal Investigator |
DOI Toshio The University of Tokushima, School of Medicine, Professor, 医学部, 教授 (60183498)
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| Co-Investigator(Kenkyū-buntansha) |
MIZUNO Akira The University of Tokushima, Medical School Hospital, Instructor, 医学部附属病院, 助手 (80219641)
NOMA Yoshihiko The University of Tokushima, Medical School Hospital, Assistant Professor, 医学部附属病院, 講師 (10218349)
KUWAJIMA Masamichi The University of Tokushima, School of Medicine, Associate Professor, 医学部, 助教授 (00205262)
TSUKAGUCHI Hiroyasu The University of Tokushima, School of Medicine, Instructor, 医学部, 助手 (60335792)
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| Project Period (FY) |
2000 – 2002
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| Keywords | mesangial cell / proliferation / Gas 6 / growth factor / warfarin / STAT3 / glomerulosclerosis / vitamin K |
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| Research Abstract |
Mesangial cell proliferation is a general characteristic of a variety of glomerular injuries. Growth arrest gene 6 (Gas 6) was one of vitamin K-dependent proteins, which was reported that the γ-carboxylation of Gas 6 is essential for its receptor-binding and growth-promoting activities in cells. The present study shows the role of Gas 6 for development of glomerular injury. Gas 6 is a new autocrine growth factor of mesangial cells. We examined the role of Gas 6/Axl in vivo in an experimental anti-Thy1 glomerulonephritis. The expression of Gas 6 was markedly increased in glomeruli in the model and the administration of warfarin significantly inhibited mesangial proliferation and the increased Gas 6 expression. The administration of Axl-extracellular domain (receptor for Gas 6) also inhibited mesangial cell proliferation. Gas 6 induced mesangial cell proliferation via latent transcription factor STAT3 in vitro and in vivo. To investigate these findings, we constructed Gas 6-/- mice and examined the role of it in accelerated nephrotoxic nephritis. Gas 6-/- mice showed less proteinuria, glomerular cell proliferation, glomerulosvlerosis and crescent formation than wild-type nephritis. These data indicate that Gas 6 contributes to glomerular injury and the progression of glomerular sclerosis.
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