miR-let-7d-HMGA2通路调控缺氧诱导的类风湿关节炎滑膜成纤维样细胞增殖  

miR-let-7d-HMGA2 signaling regulates hypoxia-induced cell proliferation of fibroblast-like synoviocytes from patients with rheumatoid arthritis

作　　者：虞珊珊[1] 李静[1] 谭琪[1] 丁梦蕾[1] 宗明[1] 范列英[1] YU Shanshan;LI Jing;TAN Qi;DING Menglei;ZONG Ming;FAN Lieying(Clinical Laboratory,Shanghai East Hospital,School of Medicine,Tongji University,Shanghai 200120,China)

机构地区：[1]同济大学附属东方医院检验科,上海200120

出　　处：《同济大学学报（医学版）》2024年第1期17-23,共7页Journal of Tongji University(Medical Science)

基　　金：国家自然科学基金面上项目(81971535);上海市浦东新区卫生系统优秀青年医学人才培养计划(PWRq2020-21);上海市“医苑新星”青年医学人才培养计划(YYXX202101)。

摘　　要：目的 研究缺氧在类风湿关节炎(rheumatoid arthritis,RA)滑膜成纤维样细胞(fibroblast-like synoviocytes,FLS)增殖中的作用及机制。方法 采用HE染色法检测RA和对照骨关节炎(osteoarthritis,OA)滑膜组织FLS增生情况。分离原代RA-FLS并采用流式细胞术鉴定;将RA-FLS置于常氧(21%O_(2))或缺氧环境(3%O_(2))中培养,CCK-8法检测细胞增殖水平的变化,RT-PCR检测miR-let-7d表达的变化。通过类似物或抑制物改变miR-let-7d的表达,观察其对RA-FLS增殖、凋亡的影响;探究miR-let-7d靶基因在缺氧诱导的RA-FLS增殖中的作用。结果 FLS在RA滑膜中增生明显,在缺氧环境下RA-FLS增殖加快,miR-let-7d表达水平降低;过表达miR-let-7d抑制RA-FLS增殖,但对细胞凋亡水平无明显影响;进一步的研究证实miR-let-7d靶基因HMGA2参与缺氧诱导的RA-FLS增殖。结论 miR-let-7d-HMGA2通路调控缺氧诱导的RA-FLS增殖。Objective To investigate the mechanisms of hypoxia-induced cell proliferation of rheumatoid arthritis fibroblast-like synoviocytes(RA-FLS).Methods FLS proliferation in the synovium tissues from patients with RA and osteoarthritis(OA) was detected by hematoxylin-eosin(HE) staining.Primary RA-FLSs were isolated and identified by flow cytometry.RA-FLS was cultured under normoxia(21%O_2) or hypoxia(3%O_2) condition,and CCK-8 assay was used to detect cell proliferation.The expression of miR-let-7d in FLS was detected with RT-PCR.The miR-let-7d mimic and inhibitor were transfected to RA-FLS,respectively.The role of HMGA2 gene in hypoxia-induced proliferation of RA-FLS was also investigated.Results Compared in OA synovium,the proliferation of FLS in RA synovium was increased significantly.Increased proliferation and down-regulation of miR-let-7d expression was found in RA-FLS under hypoxic environments.Overexpression of miR-let-7d inhibited RA-FLS proliferation,but had no effect in the apoptosis of RA-FLS.Further study indicated that,HMGA2 was a target gene of miR-let-7d in RA-FLS,and was found to be involved in hypoxia-induced proliferation of RA-FLS.Conclusion The miR-let-7d-HMGA2 signaling pathway may be involved in the proliferation of RA-FLS under hypoxia condition.

关 键 词：类风湿关节炎 滑膜成纤维样细胞 缺氧 miR-let-7d HMGA2 

分 类 号：R593.2[医药卫生—内科学]