Lu Wei, Yu Sheng-You, Wang Li-Na, Ou Qiao-Qun, Liu Yuan-Chun, Yu Li
Department of Pediatrics, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510630, China; Department of Pediatrics, Guangzhou First People's Hospital, South China University of Technology, Guangzhou, Guangdong 510180, China.
Department of Pediatrics, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, GuangZhou, GuangDong, China.
Crit Rev Eukaryot Gene Expr. 2025;35(5):69-80. doi: 10.1615/CritRevEukaryotGeneExpr.2025058852.
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.
足细胞损伤促进各种肾脏疾病的进展。本研究旨在探讨甘草酸（GL）对足细胞损伤的影响。采用嘌呤霉素氨基核苷（PAN）建立体外足细胞损伤模型。应用高通量测序分析差异表达基因（DEG）。使用京都基因与基因组百科全书分析DEG的富集情况。采用蛋白质免疫印迹法和逆转录定量PCR检测基因表达。采用酶联免疫吸附测定法检测细胞因子释放。采用乳酸脱氢酶测定法检测细胞毒性。采用末端脱氧核苷酸转移酶dUTP缺口末端标记法和流式细胞术检测足细胞死亡情况。我们发现，暴露于PAN后的DEG在炎症信号和自噬中富集。然而，GL处理抑制了促炎细胞因子的释放。GL处理消除了PAN的作用，并上调了磷酸化的unc-51样自噬激活激酶1、Beclin1、自噬相关蛋白5、LC3B/A、溶酶体相关膜蛋白2，而下调了聚集体蛋白1和gasdermin D。此外，GL处理抑制了PAN诱导的细胞毒性以及足细胞的焦亡。然而，3-甲基腺嘌呤介导的自噬抑制促进了足细胞的炎症和焦亡。总之，GL对PAN诱导的足细胞损伤具有保护作用。GL介导的自噬激活抑制了足细胞的炎症和焦亡。因此，GL可能是一种治疗足细胞损伤的策略。
