REGULATING MACROPHAGE & MESANGIAL CELL BY DIABETIC ECM

糖尿病肾病是导致终末期肾病的主要原因。 美国。弥漫性系膜扩张是糖尿病的主要组成部分 肾病。通过排挤开放的毛细血管环，这种系膜扩张 最终导致终末期肾功能衰竭。这项提案将尝试 以显示糖尿病如何导致系膜扩张。公安部最近 发现糖尿病与一种新的特异性疾病的丧失有关 抑制剂(Inhib)，MW&GT；8,000。他认为--抑制通常是根深蒂固的 在肾脏的系膜细胞外基质中。抑制素可预防 系膜基质过度扩张。在糖尿病患者中，抑制素缺失或 不起作用。这会导致系膜过度扩张。 最终导致肾功能衰竭。 提议的实验的具体目标如下。I)纯化抑制素。 Ii)制备抗抑制蛋白的单抗。三)确定原因 抑制蛋白在糖尿病肾小球系膜中不起作用。四)确定 抑制因子对系膜细胞基质生成和增殖的影响。 V)使用单抗确定小鼠的器官分布 抑制素在正常和糖尿病小鼠中的表达，并比较其分子水平 这些小鼠体内抑制素的特性。 通过了解抑制蛋白的生物化学和生物学，以及它在 糖尿病肾病，治疗这一主要原因的新方法 肾功能衰竭可能最终发展为肾功能衰竭。

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.