PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: Recent results showed that damage to endothelial cells may alter endothelial-podocyte interaction and induces nephrin loss, a main cause of proteinuria.
PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: Recent results showed that damage to endothelial cells may alter endothelial-podocyte interaction and induces nephrin loss, a main cause of proteinuria.
Authors: Xuezhu Li; Peter Y Chuang; Vivette D D'Agati; Yan Dai; Rabi Yacoub; Jia Fu; Jin Xu; Oltjon Taku; Prem K Premsrirut; Lawrence B Holzman; John Cijiang He Journal: J Am Soc Nephrol Date: 2015-02-02 Impact factor: 10.121
Authors: Timo P Hiltunen; Kati M Donner; Antti-Pekka Sarin; Janna Saarela; Samuli Ripatti; Arlene B Chapman; John G Gums; Yan Gong; Rhonda M Cooper-DeHoff; Francesca Frau; Valeria Glorioso; Roberta Zaninello; Erika Salvi; Nicola Glorioso; Eric Boerwinkle; Stephen T Turner; Julie A Johnson; Kimmo K Kontula Journal: J Am Heart Assoc Date: 2015-01-26 Impact factor: 5.501