实用医学杂志2025,Vol.41Issue(9):1285-1292,8.DOI:10.3969/j.issn.1006-5725.2025.09.003
miRNA-155-5P靶向调控SOCS1调节JAK2/STAT3信号通路对狼疮性肾炎肾脏损伤的影响
MiRNA-155-5p aggravates renal injury in lupus nephritis by targeting OCS1 to regulate the JAK2/STAT3 signaling pathway
摘要
Abstract
Objective To investigate the effect and mechanism of miR-155-5p targeting suppressor of cytokine signaling 1(SOCS1)in regulating the Janus kinase 2(JAK2)/signal transducer and activator of transcrip-tion 3(STAT3)signaling pathway in renal injury associated with lupus nephritis(LN).Methods Thirty female MRL-faslpr lupus model mice were randomly divided into five groups(n=6 per group):the model group,the antagomir NC group,the miR-155-5p antagomir group,the miR-155-5p antagomir+shRNA control group,and the miR-155-5p antagomir+SOCS1 shRNA group.The mice were treated with adeno-associated virus vectors carrying miR-155-5p antagomir,antagomir NC,SOCS1 shRNA,or shRNA control.Additionally,six age-matched C57BL/6 mice served as a control group and received an equivalent volume of saline.Serum blood urea nitrogen(BUN)and creatinine(Scr)levels,renal histopathological changes,and the expression levels of miR-155-5p,SOCS1,phosphorylated JAK2(p-JAK2),and phosphorylated STAT3(p-STAT3)in renal tissues were evaluated.Results Compared with the normal group,the model group exhibited significantly elevated levels of BUN,Scr,miR-155-5p,p-JAK2,and p-STAT3 proteins in the kidneys(P<0.01),while the expression level of SOCS1 was markedly reduced(P<0.01).Compared with both the model group and the antagomir NC group,the miR-155-5p antagomir group showed decreased levels of BUN,Scr,miR-155-5p,p-JAK2,and p-STAT3 proteins(P<0.01),along with a significant increase in SOCS1 expression(P<0.01).Similarly,compared with the miR-155-5p antagomir group and the miR-155-5p antagomir+shRNA control group,the miR-155-5p antagomir+SOCS1 shRNA group demon-strated significantly higher levels of BUN,Scr,miR-155-5p,p-JAK2,and p-STAT3 proteins(P<0.01),while SOCS1 expression was notably decreased(P<0.01).Renal pathology analysis revealed that,compared to the normal group,the model group exhibited glomerular atrophy,extensive infiltration of inflammatory cells in the renal tubulointerstitial region,and partial renal tubular necrosis.In contrast,the miR-155-5p antagomir group showed marked improvements in glomerular atrophy,tubular necrosis,and inflammatory cell infiltration compared with the model group and antagomir NC group.Furthermore,compared with the miR-155-5p antagomir group and the miR-155-5p antagomir+shRNA control group,the miR-155-5p antagomir+SOCS1 shRNA group exhibited more severe glomerular atrophy,tubular necrosis,and inflammatory cell infiltration.Conclusion MiR-155-5p exacerbates renal damage in MRL-faslpr lupus model mice by targeting SOCS1,potentially through the activation of the JAK2/STAT3 signaling pathway.关键词
狼疮性肾炎/miR-155-5p/细胞因子信号传导抑制蛋白1/JAK2/STAT3信号通路Key words
lupus nephritis/miR-155-5p/suppressor of cytokine signaling 1/JAK2/STAT3 signal-ing pathway分类
中医学引用本文复制引用
林爱桃,黄志敏,张知英,付庭娜,陆良喜,刘晓羽,江旖旎,赵蕾蕾,吴金玉..miRNA-155-5P靶向调控SOCS1调节JAK2/STAT3信号通路对狼疮性肾炎肾脏损伤的影响[J].实用医学杂志,2025,41(9):1285-1292,8.基金项目
国家自然科学基金项目(编号:81960866,82160878) (编号:81960866,82160878)
国家中医药管理局高水平中医药重点学科建设项目(编号:zyyzdxk-2023166) (编号:zyyzdxk-2023166)
广西自然科学基金项目(编号:2023GXNSFAA026211) (编号:2023GXNSFAA026211)
中医学广西一流学科(编号:桂教科研[2022]1号) (编号:桂教科研[2022]1号)