Acidic preconditioning induced intracellular acid adaptation to protect renal injury via dynamic phosphorylation of focal adhesion kinase-dependent activation of sodium hydrogen exchanger 1

作者：Annan Chen, Jian Zhang, Zhixin Yan, Yufei Lu, Weize Chen, Yingxue Sun, Qiuyu Gu, Fang Li, Yan Yang, Shanfang Qiu, Xueping Lin, Dong Zhang, Jie Teng, Yi Fang, Bo Shen, Nana Song, Xiaoqiang Ding · 发表于：Cell Communication and Signaling · 年份：2024 · DOI：10.1186/s12964-024-01773-w · 被引用次数：6 · 研究领域：Ion Transport and Channel Regulation、Cardiac Ischemia and Reperfusion、Hydrogen's biological and therapeutic effects

Disruptions in intracellular pH (pH i ) homeostasis, causing deviations from the physiological range, can damage renal epithelial cells. However, the existence of an adaptive mechanism to restore pH i to normalcy remains unclear. Early research identified H + as a critical mediator of ischemic preconditioning (IPC), leading to the concept of acidic preconditioning (AP). This concept proposes that short-term, repetitive acidic stimulation can enhance a cell’s capacity to withstand subsequent adverse stress. While AP has demonstrated protective effects in various ischemia-reperfusion (I/R) injury models, its application in kidney injury remains largely unexplored. An AP model was established in human kidney (HK2) cells by treating them with an acidic medium for 12 h, followed by a recovery period with a normal medium for 6 h. To induce hypoxia/reoxygenation (H/R) injury, HK2 cells were subjected to hypoxia for 24 h and reoxygenation for 1 h. In vivo, a mouse model of IPC was established by clamping the bilateral renal pedicles for 15 min, followed by reperfusion for 4 days. Conversely, the I/R model involved clamping the bilateral renal pedicles for 35 min and reperfusion for 24 h. Western blotting was employed to evaluate the expression levels of cleaved caspase 3, cleaved caspase 9, NHE1, KIM1, FAK, and NOX4. A pH-sensitive fluorescent probe was used to measure pH i , while a Hemin/CNF microelectrode monitored kidney tissue pH. Immunofluorescence staining was performed to vis...