1998 Fiscal Year Final Research Report Summary
Identification and fuctional analysis of genes that promote progression of glomerulosclerosis and investingation of regulatory mechantsm of the gene expression.
| Project/Area Number |
08671278
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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 |
Kidney internal medicine
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| Research Institution | Niigata University |
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Principal Investigator |
ARAKAWA Masaaki Niigata University, President, 学長 (80069012)
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| Co-Investigator(Kenkyū-buntansha) |
UENO Mitsuhiro Niigata Univ.Hospital, Assistant, 医学部附属病院, 助手 (90260546)
NARITA Ichiei Niigata Univ.Medical School, Assistant, 医学部, 助手 (20272817)
NISHI Shin-ichi Niigata Univ.Hospital, Associate Professor, 医学部附属病院, 助教授 (70251808)
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| Project Period (FY) |
1996 – 1998
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| Keywords | cnronic glomerulonephritis / glomerulosclrerosis / experimental glomerulonephritis / gene / angiotensin II receptor antagonist / dibetic nephropathy / PAI-1 gene polymorphism / Apo E gene polymorphism |
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| Research Abstract |
The molecular mechanisms, in which acute and basically self-limited glomerular injury advance to chronic and progressive glomerulosclerosis, is unknown. We tried to identify genes expressed predominantly in the kidney of chronic and progressive glomeruloscierosis but less in acute and transient glomerulonephritis. Progressive glomerulosclerosis was induced in rats by unilateral nephrectomy followed by monoclonal anti-Thy 1 .1 antibody (OX-7) injection (Nx). We have identified genes expressed predominantly in chronic glomerulosclerosis by subtraction hybridization of cDNAs from Nx with an excess amount of those from Sham operated rats. These genes may play important roles in the process which promotes initial glomerular injury to result in chronic and progressive glomerulosclerosis.
We have reported that treatment with Angiotensin II type 1 receptor antagonist (AT1Ra) reduced proteinuria and morphological change in Nx rats. Also, AT1Ra inhibited binding activity of nuclear proteins to TGF-beta control element (TCE) and reduced alpha-smooth muscle actin expression. which is well known as a marker of kidney fibrosis. We concluded that AT1Ra reduced the activity of TCE.which exists in the promotor lesion of alpha-SMC gene.
We also studied morphologically a large number of kidney biopsy specimens, and reported that tubulointerstitial lesion was important as glomerular lesion in the progression of diabetic glomerulosclerosis.
To investigate the genetic background for occurrence of nephropathy in diabetic patients. we analyzed gene polymorphism of plasminogen activator inhibitor-1, ACE, and apolipoprotein E in NIDDM patients. We have reported that PAI-l and ACE gene polymorphism are associated with the risk of. major artery complications and that apoE4 allel is a protective factor for nephropathy.
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