Glycyrrhizin Alleviates Puromycin Aminonucleoside-Induced Podocyte Injury via Regulating Autophagy and GSDMD-Dependent Pyroptosis.

Abstract

Podocyte damage contributes to the progression of various renal diseases. This study aimed to investigate the effects of glycyrrhizin (GL) on podocyte injury. Puromycin aminonucleoside (PAN) was used to establish podocyte injury model in vitro. High throughput sequencing was applied for analyzing the differentially expressed genes (DEGs). Kyoto Encyclopedia of Genes and Genomes was used to analyze the enrichment of DEGs. Gene expression was detected using Western blot and reverse transcription-quantitative PCR. The cytokine release was detected using enzyme-linked immunosorbent assay. Cytotoxicity was detected using lactate dehydrogenase assay. The death of podocytes was detected using terminal deoxynucleotidyl transferase dUTP nick-end labeling assay and flow cytometry. We found that the DEGs after exposure to PAN were enriched in inflammatory signaling and autophagy. However, GL treatment suppressed the release of proinflammatory cytokines. GL treatment abrogated the effects of PAN and upregulated phosphorylated unc-51 like autophagy activating kinase 1, Beclin1, autophagy related 5, LC3B/A, lysosomal associated membrane protein 2, whereas downregulated sequestosome 1 and gasdermin D. Moreover, GL treatment suppressed the cytotoxicity induced by PAN as well as the pyroptosis of podocytes. However, 3-Methyladenine-mediated autophagy inhibition promoted the inflammation and pyroptosis of podocytes. In summary, GL exerts protective effects on PAN-induced podocyte injury. GL-mediated activation of autophagy suppresses inflammation and pyroptosis of podocytes. Therefore, GL may be a therapeutic strategy for podocyte injury.