Proximal tubular MBD2 promotes autophagy to drive the progression of AKI caused by vancomycin via regulation of miR‐597‐5p/S1PR1 axis

• DOI: 10.1096/fj.202301500r
• Publication Date: 2024-04-05T15:09:15Z
• Authors: Yong Guo; Dengke Wu; Xiaozhou Li; Juan Wang; Huiling Li; Yijian Li; Dan Luo; Feng Yi; Dongshan Zhang
• Keywords: S1PR1

Abstract Our recent investigation has indicated that the global deletion of MBD2 can mitigate progression AKI induced by VAN. Nevertheless, role and regulatory mechanisms proximal tubular in this pathophysiological process have yet to be elucidated. preceding revealed autophagy played a crucial advancing Consequently, we postulated present tubule could upregulate autophagic expedite onset AKI. In study, found for first time mediated production Through utilization miRNA chip analysis, mechanistically demonstrated initiates activation miR‐597‐5p through promoter demethylation. This leads suppression S1PR1, which results induction apoptosis renal cells. Besides, PT‐MBD2‐KO reduced attenuate VAN‐induced via regulation miR‐597‐5p/S1PR1 axis, was reversed rapamycin. Finally, overexpression aggravated diminished autophagy‐deficient mice (PT‐Atg7‐KO). These data demonstrate facilitated axis subsequently instigated apoptosis. The potentiality being target established.