1994 Fiscal Year Final Research Report Summary
Molecular analysis of type IV collagen accumulation in diabetic nephropathy
| Project/Area Number |
05670853
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
内分泌・代謝学
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
KIKKAWA Ryuichi Shiga University of Medical Science, Third Department of Medicine, Associate Professor, 医学部, 助教授 (50093406)
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| Project Period (FY) |
1993 – 1994
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| Keywords | Diabetic nephropathy / Type IV collagen / PKC / MAP kinase / vasoactive substance / mRNA / 血管作働性物質 |
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| Research Abstract |
The mesangial expansion in glomerulis considered to be a cardinal lesion of diabetic nephropathy. The lesion is caused by the accumulation of various matrix proteins, especially of type IV collagen. So, it is important to know how type IV collagen accumulate in mesangial area in order to clarify the pathogenesis of diabetic nephropathy.
We have previous published that high concentration of glucose increases type IV collagen production in glomerular mesangial cells via its metabolic effect. In an attempt to investigate the mehanism why glucose increases type IV collagen production, the linkage between type IV collagen production and metabolic consequences to high concentration of glucose was analyzed in rat cultured mesangial cells. High concentration of glucose caused significant activation of protein kinase C (PKC) as well as of mitogen-associated protein (MAP) kinase. Various vasoactive substances, which are able to activate PKC and MAP kinase, are observed to stimulate type IV collagen production. However, any change in mRNA level for type IV collagen was not detected by northern blotting using VI (alpha_1) cDNA in mesangial cells cultured under high glucose condition. mRNAs for MMP-2 and -9, which were responsible for degrading type IV cllagen were neither changed in those experiments.
It is concluded from these results that glucose may activate PKC and MAP kinase, and may in turn stimulate type IV collagen production, which might be associated with the accumulation of type IV collagen in diabetic glomeruli.
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