Department of Nephrology, Taizhou People's Hospital, The Fifth Affiliated Hospital of Nantong University, Taizhou, China.
Department of Nephrology, Changzheng Hospital, Second Military Medical University, Shanghai, China.
Ren Fail. 2021 Dec;43(1):556-565. doi: 10.1080/0886022X.2021.1902821.
Aldosterone exerts an enormous function on proximal tubular cells (PTC) senescence, which is a common pathomechanism contributing to renal dysfunction. Numerous studies have shown that oxidative stress is deeply involved in the pathophysiologic processes of chronic kidney diseases. The study aims to investigate whether autophagy could regulate the process of senescence through oxidative stress in PTC both and . Our results suggested that aldosterone treatment increased the senescence and oxidative stress as evidenced by increased percent of SA-β-Gal positive cells, reactive oxygen species level, expression of NADPH oxidase 4 (NOX4) rather than NOX2, and the up-regulation of p21 in cultured PTC. Furthermore, the alternation of the expression of p62 and LC3-II/LC3-I demonstrated that aldosterone treatment remarkably influenced autophagic flux. NOX4 siRNA treatment or autophagy induction with rapamycin reduced the oxidative stress and senescence in aldosterone-induced PTC. On the contrary, inhibition of autophagy with chloroquine worsened these changes. Similar results were further confirmed . Our results suggested that autophagy may become a realistic therapeutic strategy against aldosterone-induced PTC injury improving oxidative stress.
醛固酮对近端肾小管细胞 (PTC) 衰老有巨大影响，这是导致肾功能障碍的常见病理机制。大量研究表明，氧化应激深人参与慢性肾脏病的病理生理过程。本研究旨在探讨自噬是否可以通过氧化应激调节 PTC 中的衰老过程。我们的结果表明，醛固酮处理增加了衰老和氧化应激，表现为 SA-β-Gal 阳性细胞的百分比增加、活性氧水平升高、NADPH 氧化酶 4 (NOX4) 而非 NOX2 的表达增加，以及培养的 PTC 中 p21 的上调。此外，p62 和 LC3-II/LC3-I 的表达变化表明，醛固酮处理显著影响自噬流。用 NOX4 siRNA 处理或用雷帕霉素诱导自噬减少了醛固酮诱导的 PTC 中的氧化应激和衰老。相反，用氯喹抑制自噬会加重这些变化。进一步证实了类似的结果。我们的结果表明，自噬可能成为一种针对醛固酮诱导的 PTC 损伤改善氧化应激的现实治疗策略。
