High glucose-altered gene expression in mesangial cells - Actin-regulatory protein gene expression is triggered by oxidative stress and cytoskeletal disassembly
High glucose-altered gene expression in mesangial cells - Actin-regulatory protein gene expression is triggered by oxidative stress and cytoskeletal disassembly
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DOI：
10.1074/jbc.m109172200
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发表时间：
2002-03-22
影响因子：
4.8
通讯作者：
Brady, HR
中科院分区：
文献类型：
--
作者：
Clarkson, MR;Murphy, M;Brady, HR
高细胞外葡萄糖在糖尿病肾病的病理生理中起着关键作用。在这里，我们报告了200个基因，用抑制减法杂交鉴定，当人系膜细胞在体外高环境葡萄糖中繁殖时，这些基因的差异表达。鉴定的主要功能基因类别包括细胞外基质蛋白代谢调节剂和产物，细胞生长和周转调节剂，以及一组肌动蛋白细胞骨架调节蛋白。肌动蛋白细胞骨架分解是糖尿病肾病的一个显著特征。高糖对肌动蛋白细胞骨架调控基因表达的诱导作用被活性氧生成抑制剂羰基氰化物间氯苯腙减弱，而不被蛋白激酶C抑制剂GF 109203X减弱，并且不被转化生长因子β的加入所模仿。在细胞松弛素d破坏系膜细胞肌动蛋白细胞骨架后，还观察到肌动蛋白细胞骨架调节基因的表达增强。总的来说，这些结果表明，编码肌动蛋白细胞骨架调节蛋白的基因的诱导(a)是糖尿病肾病系膜细胞转录组反应的重要组成部分，(b)依赖于氧化应激，不依赖于蛋白激酶C和转化生长因子- β。代表了肌动蛋白细胞骨架分解的适应性反应。
High extracellular glucose plays a pivotal role in the pathophysiology of diabetic nephropathy. Here we report 200 genes, identified using suppression-subtractive hybridization, that are differentially expressed when human mesangial cells are propagated in high ambient glucose in vitro. The major functional classes of genes identified included modulators and products of extracellular matrix protein metabolism, regulators of cell growth and turnover, and a cohort of actin cytoskeleton regulatory proteins. Actin cytoskeletal disassembly is a prominent feature of diabetic nephropathy. The induction of actin cytoskeleton regulatory gene expression by high glucose was attenuated by the inhibitor of reactive oxygen species generation, carbonyl cyanide m-chlorophenylhydrazone but not by the protein kinase C inhibitor GF 109203X and was not mimicked by the addition of transforming growth factor beta. Enhanced expression of actin cytoskeleton regulatory genes was also observed following disruption of the mesangial cell actin cytoskeleton by cytochalasin D. In aggregate, these results suggest that the induction of genes encoding actin cytoskeleton regulatory proteins (a) is a prominent component of the mesangial cell transcriptomic response in diabetic nephropathy and (b) is dependent on oxidative stress, is independent of protein kinase C and transforming growth factor-beta, and represents an adaptive response to actin cytoskeleton disassembly.