Sevoflurane activates MEF2D-rnediated Wnt/β-catenin signaling pathway via microRNA-374b-5p to affect renal ischemia/reperfusion injury

Background: The inhaled sevoflurane (Sev) has been demonstrated to protect multiple organs against ischemia/reperfusion injury (IRI). However, the mechanisms of Sev in renal IRI remain largely unknown. This study intends to explore the effect of Sev on renal IRI and the molecular mechanism behind. Methods: Following Sev preconditioning, a mouse model with renal IRI was established. The effects of Sev on IRI in mice were assessed by BUN, Scr, MDA and SOD kits, Western blot, HE staining, and TUNEL. Subsequently, we performed microarray analysis on renal tissues from mice with Sev to identify differentially expressed microRNAs (miRNAs). Then, the mice were treated with agomiR-374b-5p combined with Sev to observe the renal histopathology after IRI. The targeting mRNA of miR-374b-5p was verified using bioinformatics analysis and dual-luciferase assay, followed by KEGG enrichment analysis. Rescue experiments were implemented with simultaneous miR-374b-5p and MEF2D overexpression to detect renal histopathology and Wnt/beta-catenin pathway activity in the mice. Results: Sev significantly reduced the levels of BUN and Scr in mouse serum, prevented cell apoptosis, decreased MDA content and increased SOD levels in renal tissues. Moreover, Sev downregulated the miR-374b-5p expression in the renal tissues. Overexpression of miR-374b-5p attenuated the protective effects of Sev on mouse renal tissues. miR-374b-5p targeted MEF2D and blocked the Wnt/beta-catenin pathway. Overexpression of MEF2D activated the Wnt/beta-catenin pathway and attenuated the supporting effects of miR-374b-5p on renal IRI. Conclusion: Sev promotes MEF2D and activates the Wnt/beta-catenin pathway through inhibition of miR-374b-5p expression to affect renal IRI.