MYDGF Regulates Apoptotic Signaling to Mitigate Renal Ischemia-Reperfusion Injury and Enhance Chemotherapy Sensitivity.

Abstract

Background: Chemotherapy sensitivity in renal carcinoma may be influenced by renal ischemia-reperfusion injury (RIRI). This study elucidates the underlying mechanism by investigating the regulatory role of MYDGF. Methods: The public dataset was downloaded, and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were used to analyze functional and pathway enrichment of genes in the most significant modules. MitoTracker Green and MitoSOX were used to assess mitochondrial activity and superoxide production in oxygen-glucose deprivation/reoxygenation (OGD/R)-treated renal proximal tubular epithelial cells (RPTECs), with or without MYDGF treatment. Reactive oxygen species production and apoptosis were further analyzed through flow cytometry. A mouse model of RIRI was established and treated with MYDGF, followed by kidney evaluation after 24 h. Histological damage was assessed using hematoxylin-eosin and Masson staining in both RIRI mice and IR-induced patients with AKI. Immunohistochemistry and quantitative real-time polymerase chain reaction were performed to evaluate MYDGF, BCL2, and BAX expression levels in renal tissues. Results: A total of 557 differentially expressed genes were identified. GO and KEGG analyses revealed significant enrichment in oxidative phosphorylation and apoptosis pathways, both of which are relevant to chemosensitivity. MYDGF treatment significantly inhibited apoptosis, enhanced mitochondrial function, and reduced superoxide production in OGD/R-treated RPTECs. In vivo, MYDGF reduced tubular apoptosis and protected against kidney injury, as shown by TUNEL and Masson staining. Notably, MYDGF increased BCL2 and decreased BAX expression both in vitro and in vivo, suggesting an antiapoptotic shift. These changes may contribute not only to protection from RIRI but also to increased susceptibility of damaged renal cells to chemotherapy-induced apoptosis by maintaining mitochondrial integrity. Conclusions: Regulation of apoptotic signaling by MYDGF attenuates ischemia-reperfusion injury and improves chemotherapy outcomes in advanced renal carcinoma.