LAUSR

Renal ischemia-reperfusion injury (I/RI) has been classified as a detrimental health concern that always exacerbates acute kidney injury (AKI). Previously, total glucosides of paeony (TGP) have been reported to relieve AKI. This study sought to analyze the effect of TGP on AKI. The TCMSP database was used to predict the potential targets of TGP. Bilateral renal I/RI-induced AKI models and HK-2 cell hypoxia/reoxygenation (H/R) models were subsequently established. HLA complex group 18 (HCG18) expression was detected using RT-qPCR and overexpressed in the H/R cells, followed by the examination of cell viability, autophagosomes, and apoptosis. Subcellular localization of HCG18 was detected using the nuclear/cytosol fractionation assay. The binding relationships between HCG18 and miR-16-5p, and miR-16-5p and Bcl-2 were verified using a combination of dual-luciferase assay, RNA immunoprecipitation assay, and RNA pull-down. Serum creatinine (S-Cr), blood urea nitrogen (BUN), and KIM-1 contents in AKI mice were examined using ELISA, and the pathological modifications in renal tissue and apoptosis were assessed using hematoxylin and eosin staining and TUNEL staining. HCG18 was downregulated in the in vitro and in vivo models. Our findings denoted that TGP promoted HK-2 cell autophagy and proliferation and inhibited inflammation and apoptosis by upregulating HCG18, thus alleviating AKI. HCG18 was predominantly localized in the cytoplasm. HCG18 could competitively bind to miR-16-5p. Additionally, miR-16-5p overexpression reversed the stimulative effect of HCG18 on HK-2 cell autophagy. miR-16-5p targeted Bcl-2. Bcl-2 overexpression reversed the inhibitory effect of miR-16-5p on HK-2 cell autophagy. TGP treatment reduced the S-Cr, BUN, and KIM-1 contents, and alleviated renal tubular injury and apoptosis in I/RI mice by upregulating HCG18. Briefly, our study elicited that TGP inhibited miR-16-5p and promoted Bcl-2 by upregulating HCG18, thus promoting autophagy and alleviating AKI in I/RI mice.