Amelioration of Albuminuria in ROCK1 Knockout Mice with Streptozotocin-Induced Diabetic Kidney Disease
Publication in refereed journal


摘要Background: Although blockade of Rho kinase with pharmacologic inhibitors ameliorates renal fibrosis and diabetic kidney disease (DKD), the underlined mechanisms remain largely unclear. The present study tested the hypothesis that ROCK1 may regulate the early development of albuminuria via the megalin/cubilin-dependent mechanism. Methods: A DKD model was induced in ROCK1 knockout and wild-type mice by streptozotocin (STZ). The effect of deleted ROCK1 on urinary albumin excretion and the expression of megalin/cubilin were examined. In addition, the effect of blocking ROCK activities with an inhibitor (Y-27632) on tubular albumin reabsorption was tested in a normal rat tubular epithelial cell line (NRK52E) under high-glucose conditions. Expression of transforming growth factor (TGF)-beta 1, interleukin-1 beta and collagen-1 was also been examined. Results: Urinary albumin excretion was significantly increased in ROCK1 WT mice at 8 weeks after STZ injection. In contrast, mice lacking ROCK1 gene were protected against the development of albuminuria. This was associated with the protection against the loss of megalin/cubilin and an increase in TGF-beta(1), IL-1 beta, and fibrosis in the kidney. In vitro, we also found that blockade of Rho kinase with inhibitor Y-27632 prevented high-glucose-induced loss of megalin expression and an increase of TGF-beta(1), thereby increasing the absorption rate of FITC-labeled albumin by tubular epithelial cells. Conclusion: ROCK1 may play a role in the development of albuminuria in DKD by downregulating the endocytosis receptors complex -megalin/cubilin. Copyright (C) 2011 S. Karger AG, Basel
著者Zhou L, Fu P, Liu F, Huang XR, Liu F, Chen HY, Chung ACK, Shi JJ, Wei L, Lan HY
期刊名稱American Journal of Nephrology
出版社Karger Publishers
頁次468 - 475
關鍵詞Cubilin; Diabetic kidney disease; Megalin; ROCK; Tubular cells, albuminuria
Web of Science 學科類別Urology & Nephrology; UROLOGY & NEPHROLOGY

上次更新時間 2021-07-01 於 23:52