Heat shock protein expression in diabetic nephropathy
Heat shock protein expression in diabetic nephropathy
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DOI：
10.1152/ajprenal.90234.2008
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发表时间：
2008-12-01
影响因子：
4.2
通讯作者：
Gruden, Gabriella
中科院分区：
文献类型：
--
作者：
Barutta, Federica;Pinach, Silvia;Gruden, Gabriella
热休克蛋白（HSP） HSP27、HSP60、HSP70和HSP90是由细胞应激诱导产生的，在细胞保护中起关键作用。高血糖和肾小球高血压都是糖尿病肾病发病的关键决定因素，并对肾靶细胞施加细胞应激。我们研究了HSP27、HSP60、HSP70和HSP90在链脲佐菌素致糖尿病大鼠体内和体外高糖或机械拉伸下系膜细胞和足细胞的表达和磷酸化状态。分别在糖尿病发病后4、12和24周对糖尿病动物和对照动物进行研究。免疫组织化学分析显示，HSP25、HSP60和HSP72在糖尿病外髓质中过表达，而在肾小球中未见差异。同样，既不暴露于高葡萄糖，也不暴露于拉伸，会改变系膜细胞和足细胞中热休克蛋白的表达。相比之下，HSP27的磷酸化形式在糖尿病动物的肾小球足细胞中增强，体外拉伸足细胞暴露通过p38依赖机制诱导HSP27磷酸化。总之，糖尿病和糖尿病相关损伤对肾小球和髓质中HSP27、HSP60和HSP70的表达/磷酸化有差异调节，这可能影响肾细胞产生有效细胞保护反应的能力。
Heat shock protein (HSP) HSP27, HSP60, HSP70, and HSP90 are induced by cellular stresses and play a key role in cytoprotection. Both hyperglycemia and glomerular hypertension are crucial determinants in the pathogenesis of diabetic nephropathy and impose cellular stresses on renal target cells. We studied both the expression and the phosphorylation state of HSP27, HSP60, HSP70, and HSP90 in vivo in rats made diabetic with streptozotocin and in vitro in mesangial cells and podocytes exposed to either high glucose or mechanical stretch. Diabetic and control animals were studied 4, 12, and 24 wk after the onset of diabetes. Immunohistochemical analysis revealed an overexpression of HSP25, HSP60, and HSP72 in the diabetic outer medulla, whereas no differences were seen in the glomeruli. Similarly, exposure neither to high glucose nor to stretch altered HSP expression in mesangial cells and podocytes. By contrast, the phosphorylated form of HSP27 was enhanced in the glomerular podocytes of diabetic animals, and in vitro exposure of podocytes to stretch induced HSP27 phosphorylation via a P38-dependent mechanism. In conclusion, diabetes and diabetes-related insults differentially modulate HSP27, HSP60, and HSP70 expression/phosphorylation in the glomeruli and in the medulla, and this may affect the ability of renal cells to mount an effective cytoprotective response.