TRIM58通过抑制WNT/β-catenin通路参与脂多糖诱导的足细胞损伤  

TRIM58 participates in LPS-induced podocytes injury by inhibiting WNT/β-catenin signaling pathway

作　　者：于群 胡锦秀 林建功[1] 刘冰 贾磊[2] YU Qun;HU Jinxiu;LIN Jiangong;LIU Bing;JIA Lei(Department of Nephrology,Shandong Provincial Hospital Affiliated to Shandong University,Jinan 250021,China;Hospital Infection Management Office,Shandong Provincial Hospital Affiliated to Shandong University,Jinan 250021,China)

机构地区：[1]山东大学附属省立医院肾内科,济南250021 [2]山东大学附属省立医院感染管理办公室,济南250021

出　　处：《免疫学杂志》2021年第6期497-504,共8页Immunological Journal

摘　　要：目的探讨TRIM58在脂多糖(lipopolysaccharide,LPS)诱导的足细胞损伤中的作用及其分子机制。方法将体外培养的永生化人足细胞分成4组:正常对照组(Control),LPS刺激组(LPS),TRIM58过表达+LPS组(OE-TRIM58+LPS),空载体+LPS组(OE-NC+LPS)。通过ELISA检测炎性分子IL-1β、TNF-α的表达;通过real-time PCR、Western blot、免疫荧光检测足细胞Desmin、ZO-1的表达;通过Transwell检测足细胞迁移能力;通过real-time PCR、Western blot检测TRIM58的表达;通过Western blot检测调控TRIM58对β-catenin表达的影响。结果 LPS刺激后,炎性因子IL-1β、TNF-α的表达明显升高,足细胞Desmin蛋白和mRNA表达明显上调,ZO-1蛋白和mRNA表达明显下调,TRIM58的蛋白和mRNA表达下调,同时伴有β-catenin的表达升高。Transwell结果表明,LPS刺激下足细胞迁移能力明显增强。过表达TRIM58可明显减轻LPS诱导的炎性细胞因子IL-1β、TNF-α的释放,抑制上皮间充质转化和足细胞迁移能力,缓解足细胞损伤。此外,TRIM58过表达可下调LPS诱导的β-catenin的表达。结论 LPS刺激可下调TRIM58的表达,而过表达TRIM58可能通过抑制WNT/β-catenin通路,减轻LPS诱导的足细胞炎性反应和EMT,从而缓解足细胞损伤。To investigate the role of TRIM58 in LPS-induced podocytes injury,immortalized human podocytes(HPCs) were introduced and divided into control group,LPS group,TRIM58 vector+LPS group and Control vector+LPS group.The levels of inflammatory factors IL-1βand TNF-αwere detected by ELISA;the expression of Desmin and ZO-1 were detected by real-time PCR,Western blot,and immunofluorescence staining;the migration ability of cultured podocytes was measured by Transwell assay;the expression of TRIM58 was examined by real-time PCR and Western blotting,while the effects of TRIM58 onβ-catenin was detected by Western blotting.Data showed that after LPS stimulation,the level of inflammatory factors IL-1βand TNF-αwere significantly up-regulated,the protein and mRNA expressions of desmin were also significantly up-regulated,while the protein and mRNA expressions of ZO-1 were significantly down-regulated.Besides,the expression of TRIM58 was down-regulated under LPS stimulation,accompanied by an increase ofβ-catenin;Transwell results showed the migration ability of podocytes was significantly enhanced under LPS stimulation.Furthermore,overexpression of TRIM58 not only significantly attenuated the production of inflammatory factors,but inhibited epithelial-mesenchymal transition and the ability of migration,leading to the alleviation of podocyte injury.In addition,TRIM58 overexpression down-regulated the expression of LPS-inducedβ-catenin.In conclusion,TRIM58 is down-regulated in podocytes under LPS stimulation, and overexpression of TRIM58 can attenuate LPS-induced inflammatory responseand EMT by inhibiting the WNT/β-catenin pathway.

关 键 词：脂多糖 足细胞 TRIM58 Β-CATENIN 

分 类 号：R392.12[医药卫生—免疫学]