骨髓间充质干细胞来源外泌体miR-30e-5p改善高血糖诱发的肾小管上皮细胞的焦亡  

Bone marrow mesenchymal stem cell-derived exosomal miR-30e-5p ameliorates high-glucose induced renal proximal tubular cell pyroptosis

作　　者：吕佳 郝亚宁[1] 王晓培 路万虹[1] 张亚莉[1] 牛丹 LÜJia;HAO Yaning;WANG Xiaopei;LU Wanhong;ZHANG Yali;NIU Dan(Department of Nephrology,Nephrotic Hospital,The First Affiliated Hospital of Xi’an Jiaotong University Health Science Center,Xi’an 710061,China)

机构地区：[1]西安交通大学第一附属医院肾病医院肾内科,陕西西安710061

出　　处：《西安交通大学学报（医学版）》2023年第6期859-865,共7页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：陕西省重点研发计划(No.2017SF-133)。

摘　　要：目的探讨骨髓间充质干细胞外泌体(BMSC-exos)miR-30e-5p对高葡萄糖(HG)诱导的体外培养的人肾近端小管细胞(HK-2)焦亡的影响,并探索治疗糖尿病肾病(DKD)的替代方法。方法BMSC-exos分离并内化到HG处理的HK-2细胞中,测定细胞生存能力和细胞毒性。通过流式细胞仪方法评估细胞焦亡,检测miR-30e-5p、IL-1β和IL-18的表达水平,通过Western blotting蛋白质印迹分析测定焦亡相关的细胞因子蛋白。结果BMSC-exos降低了LDH、IL-1β和IL-18的分泌,改善焦亡情况,并抑制了HG诱导的HK-2细胞中的焦亡相关因子(IL-1β、胱天蛋白酶-1、GSDMD-N和NLRP3)的表达。miR-30e-5p敲除逆转了BMSC-exos对HK-2细胞焦亡的改善作用。结论BMSC-exos的miR-30e-5p抑制HG处理的HK-2细胞焦亡,这可能为治疗DKD提供一种新的策略。Objective To study the effects of miR-30e-5p from bone marrow mesenchymal stem cell-derived exosomes(BMSC-exos)on high glucose(HG)-induced HK-2 cell pyroptosis and explore an alternative strategy to manage diabetic kidney disease(DKD).Methods BMSC-exos were isolated and internalized into HK-2 cells treated with HG to measure viability and cytotoxicity.The secretion of IL-1βand IL-18 was measured by ELISA.Pyroptosis was assessed by flow cytometry.The levels of miR-30e-5p,IL-1β,and IL-18 were measured.The expression of pyroptosis-associated cytokine proteins was determined.Results BMSC-exos decreased LDH,IL-1β,and IL-18 secretion and inhibited the expression of the pyroptosis-related factors(IL-1β,caspase-1,GSDMD-N,and NLRP3)in HG-induced HK-2 cells.Moreover,miR-30e-5p depletion in BMSC-exos promoted HK-2 cell pyroptosis.Conclusion BMSC-derived exosomal miR-30e-5p inhibits caspase-1-mediated pyroptosis in HG-induced HK-2 cells,which might provide a new strategy for treating DKD.

关 键 词：焦亡 骨髓间充质干细胞 外泌体 miR-30e-5p 糖尿病性肾病 

分 类 号：R587[医药卫生—内分泌]