REGULATING MACROPHAGE & MESANGIAL CELL BY DIABETIC ECM

糖尿病肾病是糖尿病患者中终末期肾病的主要原因。 美国的弥漫性系膜扩张是糖尿病肾病的主要组成部分。 肾病通过挤出开放的毛细血管环，这种系膜扩张 最终导致终末期肾衰竭该提案将试图 来展示糖尿病如何导致系膜扩张PI最近 发现糖尿病与一种新的特异性 抑制剂（INHIB），mw> 8，000。他认为INHIB通常嵌入 在肾脏的系膜细胞外基质中。INHIB防止 系膜基质过度扩张在糖尿病中，INHIB不存在或 不起作用这导致过度的系膜扩张 最终导致肾衰竭 拟议实验的具体目标如下。I）纯化INHIB。 II）制备抗INHIB的单克隆抗体。（三）确定原因 INHIB在糖尿病肾系膜中无功能。IV）确定 INHIB对系膜细胞基质生成和增殖的影响。 V）用单克隆抗体测定大鼠肝、肾、脾、肾、脾、 INHIB在正常和糖尿病小鼠，并比较分子 这些小鼠中INHIB的特征。 通过了解INHIB的生物化学和生物学，以及它在 糖尿病肾病是糖尿病肾病的主要病因。 最终可能发展为肾衰竭。

Diabetic nephropathy is the leading cause of end stage renal disease in the United States. Diffuse mesangial expansion is a major component of diabetic nephropathy. By crowding out open capillary loops, this mesangial expansion eventually results in end-stage renal failure. This proposal will attempt to show how diabetes results in mesangial expansion. The PI has recently discovered that diabetes is associated with the loss of a novel specific inhibitor (INHIB), mw> 8,000. He believes-that INHIB is ordinarily embedded in the mesangial extracellular matrix of the kidney. INHIB prevents excessive mesangial matrix expansion. In diabetes, INHIB is absent or non-functional. This results in excessive mesangial expansion and-ultimately renal failure. The specific aims of the proposed experiments follow. I) To purify INHIB. II) To prepare monoclonal antibodies against INHIB. III) To determine why INHIB is nonfunctional in the diabetic renal mesangium. IV) To determine the effect of INHIB on mesangial cell matrix production and proliferation. V) To use the monoclonal antibodies to determine the organ distribution of INHIB in normal and diabetic mice, and to compare the molecular characteristics of INHIB in these mice. By understanding the biochemistry and biology of INHIB, and its absence in diabetic nephropathy, new therapeutic approaches to this major cause of renal failure may eventually be developed.