Resveratrol Attenuates Oxalate-Induced Renal Oxidative Injury and Calcium Oxalate Crystal Deposition by Regulating TFEB-Induced Autophagy Pathway.

Yue Wu,Shaogang Wang,Cong Li,Tao Wang,Jiaqiao Zhang,Yuchao Lu,Henglong Hu,Baolong Qin,Yang Xun

doi:10.3389/fcell.2021.638759

Abstract

The oxidative injury of renal tubular epithelial cells caused by inflammation and oxidative stress induced by hyperoxaluria is an important factor in the kidney calcium oxalate (CaOx) stone formation. Resveratrol (RSV) has been reported to reduce oxidative injury to renal tubular epithelial cells, and autophagy is critical for the protective effect of resveratrol. However, the protective mechanism of RSV in oxalate-induced oxidative injury of renal tubular cells and the role of autophagy in this process are still unclear. In our study, glyoxylic acid monohydrate-induced rats were treated with or without resveratrol, and it was detected that the overexpression of oxidant species, CaOx crystal deposition, apoptosis level, inflammatory cytokines and osteoblastic-associated protein expression were reversed by resveratrol. Additionally, Resveratrol pretreatment significantly reversed oxalate -induced decline in cell viability, cell damage, oxidant species overexpression, and osteogenic transformation in normal rat kidney epithelial-like (NRK-52E) cells. Furthermore, we found that RSV pretreatment promoted intracellular LC3II upregulation, p62 downregulation, and autophagosome formation, whereas 3-methyladenine treatment reduced this effect. Moreover, RSV induced the expression of transcription factor EB (TFEB) in the nucleus of NRK-52E cells in a concentration-dependent manner. After transfection of NRK-52E cells with TFEB siRNA, we showed that the RSV-induced increase in TFEB expression and autophagosome formation were inhibited. Simultaneously, RSV-induced NRK-52E cells protection was partially reversed. These results suggested that RSV regulates oxalate-induced renal inflammation, oxidative injury, and CaOx crystal deposition in vitro and in vivo through the activation of a TFEB-induced autophagy.

Highlights

Kidney stone disease is a recurrent and lifelong disease that causes significant health and financial burden
Compared with the control group, greater calcium oxalate (CaOx) crystal deposition occurred at the junction of the medullary and cortex of the rat kidney tissue in the glyoxylic acid monohydrate (GAM) and GAM + methyl cellulose (MC) groups, but there was no significant difference in CaOx crystal deposition between the GAM and GAM + MC groups (Figure 2A)
After RSV treatment, CaOx crystal deposition was significantly reduced in the GAM + RSV group compared with the GAM and GAM + MC groups (Figure 2A)

Summary

Introduction

Kidney stone disease is a recurrent and lifelong disease that causes significant health and financial burden. The worldwide prevalence of kidney stone ranges from 7 to 13% in North America, from 5 to 9% in Europe, and from 1 to 5% in Asia (Sorokin et al, 2017). Approximately 80% of kidney stones are calcium-containing stones (Kusmartsev et al, 2016). Numerous studies have attempted to elucidate the mechanism of kidney stone formation, the exact details remain unclear. Hyperoxaluria is a known key factor in kidney stone formation (Coe et al, 2005). Injury induced by high concentrations of oxalate in renal tubular epithelial cells is related to oxidative stress and inflammation (Tsuji et al, 2016); these conditions contribute to the crystallization of calcium oxalate (CaOx) by providing material basis for its ectopic nucleation, and facilitate the adhesion of CaOx crystals to renal tubular epithelial cells (Aggarwal et al, 2013; Khan, 2013)

Methods

Results

Conclusion