Hauser Peter V, Collino Federica, Bussolati Benedetta, Camussi Giovanni
Department of Internal Medicine and Center for Molecular Biotechnology, University of Torino, Torino, Italy.
Curr Opin Nephrol Hypertens. 2009 Jan;18(1):3-8. doi: 10.1097/MNH.0b013e32831a4713.
Nephrin, the main structural protein of the slit diaphragm, is expressed on the surface of glomerular podocytes and is critical in maintaining permselectivity and preventing proteinuria. This review focuses on the fate of nephrin in the context of endothelial injury and gives an update on the recent progress in understanding the pathomechanisms that lead to proteinuria.
The following conditions of endothelial injury were found to induce loss of nephrin.(1) Preeclampsia, in which the associated proteinuria is induced by the soluble variant of vascular endothelial growth factor, which stimulates production of endothelin 1 (ET1) in endothelial cells. ET1 in turn triggers nephrin shedding from podocytes.(2) Hypertension, in which increased levels of angiotensin II induce podocyte apoptosis and reduce nephrin expression, leading to proteinuria in rats.(3) Diabetes and high fat diet, which lead to a significant increase in inflammatory molecules and cytokines, including MCP-1, which induces changes in podocyte cytoskeleton and nephrin loss.
Recent results showed that damage to endothelial cells may alter endothelial-podocyte interaction and induces nephrin loss, a main cause of proteinuria.
Nephrin是裂孔隔膜的主要结构蛋白，表达于肾小球足细胞表面，对维持滤过选择性和预防蛋白尿至关重要。本综述聚焦于内皮损伤情况下Nephrin的命运，并介绍了在理解导致蛋白尿的发病机制方面的最新进展。
发现以下内皮损伤情况可导致Nephrin丢失。（1）子痫前期，其中相关蛋白尿由血管内皮生长因子的可溶性变体诱导产生，该变体刺激内皮细胞产生内皮素1（ET1）。ET1继而触发足细胞释放Nephrin。（2）高血压，其中血管紧张素II水平升高诱导足细胞凋亡并降低Nephrin表达，导致大鼠蛋白尿。（3）糖尿病和高脂饮食，导致包括MCP-1在内的炎症分子和细胞因子显著增加，MCP-1诱导足细胞细胞骨架改变和Nephrin丢失。
最近的结果表明，内皮细胞损伤可能改变内皮-足细胞相互作用并导致Nephrin丢失，这是蛋白尿的主要原因。
