STUDIES OF GLOMERULAR CELLS DERIVED FROM NORMAL AND TRANSGENIC MICE

肾小球硬化，细胞和细胞外基质周转增加，是 是美国肾衰竭的主要原因。模型的最新研究 对肾小球硬化(GS)的研究几乎没有提供关于 在启动和恢复过程中起关键作用的细胞异常 这种疾病的发展。这在一定程度上是由于 在活体中分离和鉴定肾小球，事实是 肾小球包含三种本地细胞类型和一组骨 骨髓来源的巨噬细胞。这对老鼠来说是一个特别的问题， 我们之所以选择研究这一物种，是因为 相当多的遗传信息。我们已经分离了单个细胞 类型，并在体外对它们进行表征。第一系列实验 研究了肾小球的表型调节问题 体外培养的肾小球系膜细胞，解决了 不同的底物，所涉及的时间范围和分子 这种调节对细胞外基质周转的影响。我们 发现肾小球系膜细胞增殖和胶原蛋白的mRNA水平 独立监管的。此外，矩阵的性质 细胞的黏附直接影响细胞的增殖和胶原基因的表达。 级别。第二个实验涉及对大分子的处理。 通过系膜细胞，因为这些细胞能够摄取 体内的免疫球蛋白。甘露糖受体(MR)，一种碳水化合物 巨噬细胞上存在的结合膜蛋白被认为是一种 系膜细胞摄取这些大细胞的机制候选 蛋白质。在受刺激的系膜细胞上发现了MR 使用白介素1α或肿瘤坏死因子α。

Glomerulosclerosis, increased cell and extracellular matrix turnover, is the leading cause of renal failure in the US. Current studies in models of glomerulosclerosis (GS) have yielded little information about the cellular abnormalities that are critical in the initiation and progression of this disease. This is due, in part, to the difficulty in isolating and characterizing glomeruli in vivo, and the fact that the glomerulus contains three indigenous cell types and a population of bone marrow-derived macrophages. This is particularly a problem with mice, a species we have chosen to study because of the availability of considerable genetic information. We have isolated the individual cell types and characterizing them in vitro. The first series of experiments examined the question of the phenotyPic modulation of glomerular mesangial cells in vitro, addressing the question of the effect of differing substrates, the time frame involved, and the molecular consequences of this modulation on extracellular matrix turnover. We found that mesangial cell proliferation and collagen mRNA levels are independently regulated. In addition, the nature of the matrix to which the cells adhered directly affected both proliferation and collagen mRNA levels. The second experiments addressed the handling of macromolecules by mesangial cells, since these cells are capable of ingesting immunoglobulins in vivo. The mannose receptor (MR), a carbohydrate binding membrane protein present on macrophages, was considered to be a candidate for the mechanism by which mesangial cells ingested these large proteins. The MR was found on mesangial cells which had been stimulated with either interleukin-1alpha or tumor necrosis factor-alpha.