STUDIES OF GLOMERULAR CELLS DERIVED FROM NORMAL AND TRANSGENIC MICE

肾小球硬化症的特征是细胞和细胞外的增加 基质周转，是美国肾衰竭的主要原因。 我们已经开发了三种本土小鼠肾小球细胞系， 类型：上皮、内皮和系膜细胞。 我们选择了老鼠 由于大量的背景基因的可用性， 信息. 我们描述了细胞的生物合成能力 分离自患有慢性进行性肾病的正常和转基因小鼠 疾病 所有三种细胞类型表达IV型胶原α链 mRNA。 肾小球系膜细胞表达高水平的1-5型IV型胶原 链以及I型和VI型胶原蛋白。 3 IV型胶原 主要存在于内皮细胞中。 内皮细胞和上皮 细胞既不表达VI型胶原也不表达I型胶原。 因此，每种细胞类型具有 对发展作出独特贡献的潜力， 肾小球硬化 我们从小鼠身上分离出细胞， 转基因编码牛生长激素（bGH），因为这些小鼠具有 一种导致死亡的弥漫性和进行性肾小球硬化 尿毒症患者。 bGH系膜细胞具有降低的细胞更新， 增加的α-1 IV型胶原mRNA水平（以及增加的 IV型胶原蛋白分泌）和转化生长因子增加 mRNA水平。 通过PCR检测，它们同时表达GH受体和bGH mRNA 分析. 所述转基因含有金属硫蛋白启动子， 由锌激活。 锌处理后，GH mRNA表达增加， 并且相应的肽是可检测的。 这些数据显示 肾小球硬化诱导系膜细胞稳定的表型改变 细胞 这些效应可以解释观察结果表明，GH是一种 在肾小球硬化症的发展中的重要许可因素， 动物模型，也可能是人。

Glomerulosclerosis is characterized by increased cell and extracellular matrix turnover and is the leading cause of renal failure in the US. We have developed lines of the three indigenous mouse glomerular cell types: epithelial, endothelial and mesangial cells. We chose mice because of the availability of considerable background genetic information. We characterized the biosynthetic capabilities of cells isolated from normal and transgenic mice with chronic progressive renal diseases. All three cell types express type IV collagen alpha chain mRNAs. Mesangial cells express high levels of 1-5 type IV collagen chains as well as types I and VI collagens. 3 type IV collagen predominates in endothelial cells. Endothelial cells and epithelial cells express neither types VI or I collagen. Thus, each cell type has the potential to make a unique contribution to development of glomerulosclerosis. We isolated cells from mice which carry a transgene coding for bovine growth hormone (bGH), since these mice have a diffuse and progressive form of glomerulosclerosis leading to death in uremia. The bGH mesangial cells have decreased cell turnover, increased alpha-1 type IV collagen mRNA levels (as well as increased type IV collagen secretion), and increased transforming growth factor mRNA levels. They express both GH receptor and bGH mRNA by PCR analysis. The transgene contains a metallothionein promoter which is activated by zinc. After zinc treatment there is an increase in GH mRNA and the corresponding peptide is detectable. These data show that glomerulosclerosis induces a stable phenotypic change in mesangial cells. These effects may explain observations suggesting that GH is an important permissive factor in the development of glomerulosclerosis in animal models, and possibly in man.