Abstract
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.
Highlights
Nephrolithiasis has a serious impact on human health and is a frequently occurring disease that has many causes, including genetic, environmental, and metabolic factors
We found calcium oxalate (CaOx) crystal deposition in the lumens of the renal tubules of nephrolithiasis patients examined by hematoxylin and eosin (H&E) staining (Figure 1A)
To test whether autophagy activity is increased in calcium oxalate nephrolithiasis tissues, the expression of critical autophagic proteins LC3 and BECN1 was evaluated by immunohistochemistry and western blot technology
Summary
Nephrolithiasis has a serious impact on human health and is a frequently occurring disease that has many causes, including genetic, environmental, and metabolic factors. Previous studies have shown that exposure of renal tubular epithelial cells (RTECs) to high concentrations of CaOx crystals leads to the production of reactive oxygen species (ROS) and oxygen free radicals and the development of oxidative stress (OS) along with injury and inflammation [4, 5]. These results indicate that peroxidatic injury of renal tubular epithelial cells caused by ROS may contribute to the development and progression of calcium oxalate kidney stones
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