Wu Yue, Xun Yang, Zhang Jiaqiao, Hu Henglong, Qin Baolong, Wang Tao, Wang Shaogang, Li Cong, Lu Yuchao
Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Cell Dev Biol. 2021 Feb 25;9:638759. doi: 10.3389/fcell.2021.638759. eCollection 2021.
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 and through the activation of a TFEB-induced autophagy.
高草酸尿症诱导的炎症和氧化应激所导致的肾小管上皮细胞氧化损伤是肾草酸钙（CaOx）结石形成的一个重要因素。据报道，白藜芦醇（RSV）可减轻肾小管上皮细胞的氧化损伤，而自噬对于白藜芦醇的保护作用至关重要。然而，RSV在草酸诱导的肾小管细胞氧化损伤中的保护机制以及自噬在此过程中的作用仍不清楚。在我们的研究中，用或不用白藜芦醇处理一水合乙醛酸诱导的大鼠，检测发现白藜芦醇可逆转氧化剂的过表达、CaOx晶体沉积、凋亡水平、炎性细胞因子和成骨相关蛋白的表达。此外，白藜芦醇预处理显著逆转了草酸诱导的正常大鼠肾上皮样（NRK-52E）细胞活力下降、细胞损伤、氧化剂过表达和成骨转化。此外，我们发现RSV预处理促进细胞内LC3II上调、p62下调和自噬体形成，而3-甲基腺嘌呤处理可降低这种作用。此外，RSV以浓度依赖性方式诱导NRK-52E细胞核中转录因子EB（TFEB）的表达。用TFEB siRNA转染NRK-52E细胞后，我们发现RSV诱导的TFEB表达增加和自噬体形成受到抑制。同时，RSV诱导的NRK-52E细胞保护作用部分被逆转。这些结果表明，RSV通过激活TFEB诱导的自噬来调节草酸诱导的肾脏炎症、氧化损伤和CaOx晶体沉积。
