The Rho kinase signaling pathway participates in tubular mitochondrial oxidative injury and apoptosis in uric acid nephropathy.

Abstract

IntroductionOxidative stress is a pathologic feature of hyperuricemia that is highly prevalent and that contributes to kidney tubular interstitial fibrosis. Rho-kinase is closely related to mitochondrial-induced oxidative stress. Herein, we designed a study to explore the expression and role of Rho-kinase in hyperuricemia nephropathy. The secondary objective was to investigate whether the Rho-kinase signaling pathway regulates hyperuricemic tubular oxidative injury and apoptosis via the mitochondrial pathway in addition to the mechanisms that are involved.Materials and methodsHK-2 cells were divided into the following five groups: normal; uric acid (UA); UA+Fasudil; UA+ROCK1 si-RNA; and UA+sc-siRNA. Rho-kinase activity, mitochondrial oxidative injury, and apoptosis-related protein levels were measured in each group. A t-test was used to analyze the difference between groups.ResultsMyosin phosphatase target subunit 1 (MYPT1) overexpression was shown in HK-2 cells, which was caused by UA. High concentrations of UA also up-regulated Rho-kinase expression and mitochondrial and apoptosis-related protein expression, while treatment with fasudil and ROCK1 si-RNA significantly attenuated these responses.ConclusionThe Rho-kinase signaling pathway participates in tubular mitochondrial oxidative injury and apoptosis via regulating mitochondrial dyneins/biogenic genes in UA nephropathy, which suggests that the mitochondrial pathway might be a potential therapeutic target for hyperuricemia nephropathy.