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Molecular analysis of type IV collagen accumulation in diabetic nephropathy

糖尿病肾病IV型胶原沉积的分子分析

基本信息

批准号：
05670853
负责人：
KIKKAWA Ryuichi
金额：
$ 1.34万
依托单位：
Shiga University of Medical Science
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

项目摘要

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.

肾小球系膜扩张被认为是糖尿病肾病的主要病变。病变是由各种基质蛋白，特别是IV型胶原蛋白的积累引起的。因此，了解IV型胶原在肾小球系膜区的聚集情况对阐明糖尿病肾病的发病机制具有重要意义。我们以前曾发表过高浓度葡萄糖通过其代谢作用增加肾小球系膜细胞中IV型胶原的产生。为了研究葡萄糖增加IV型胶原产生的机制，在大鼠培养的系膜细胞中分析了IV型胶原产生和高浓度葡萄糖的代谢后果之间的联系。高浓度的葡萄糖引起蛋白激酶C（PKC）和丝裂原相关蛋白（MAP）激酶的显著激活。观察到能够激活PKC和MAP激酶的各种血管活性物质刺激IV型胶原蛋白的产生。然而，在高糖条件下培养的系膜细胞中，使用VI（α_1）cDNA的北方印迹法未检测到IV型胶原mRNA水平的任何变化。上述结果提示，葡萄糖可激活PKC和MAP激酶，进而刺激IV型胶原的生成，这可能与IV型胶原在糖尿病肾小球的积聚有关。