Inhibition of autophagy-attenuated calcium oxalate crystal-induced renal tubular epithelial cell injury in vivo and in vitro
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Yunlong Liu1, Derong Li1, Ziqi He1, Quan Liu1, Jihua Wu1, Xiaofeng Guan1, Zhiwei Tao1 and Yaoliang Deng1
1Department of Urology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
Zhiwei Tao, email: [email protected]
Yaoliang Deng, email: [email protected]
Keywords: autophagy; calcium oxalate crystals; renal tubular epithelial cells; reactive oxygen species; autophagic vacuoles
Received: August 29, 2017 Accepted: November 15, 2017 Published: December 17, 2017
Accumulating evidence suggests that autophagy is involved in the pathophysiological processes of kidney diseases. However, the role of autophagy in the formation of calcium oxalate (CaOx) nephrolithiasis remains unclear. In this study, we investigated the effects of autophagy on renal tubular epithelial cell injury induced by CaOx crystals in vivo and in vitro. We first observed that the expression levels of LC3-II and BECN1 and number of autophagic vacuoles were markedly increased in the renal tissue of CaOx stone patients. We subsequently found that exposure of HK-2 cells to CaOx crystals could increase LC3-II and BECN1 expression as well as the number of GFP-LC3 dots and autophagic vacuoles in a dose- and time-dependent manner. In addition, our results suggest that CaOx crystals induced autophagy, at least in part, via activation of the reactive oxygen species (ROS) pathway in HK-2 cells. Furthermore, inhibition of autophagy using 3-methyladenine or siRNA knockdown of BECN1 attenuated CaOx crystal-induced HK-2 cells injury. However, enhancing autophagic activity with rapamycin exerted an opposite effect. Taken together, our results demonstrate that autophagy is essential for CaOx crystal-induced renal tubular epithelial cell injury and that inhibition of autophagy could be a novel therapeutic strategy for CaOx nephrolithiasis.
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