miR-205-5p in exosomes divided from chondrogenic mesenchymal stem cells alleviated rheumatoid arthritis via regulating MDM2 in fibroblast-like synoviocytes
miR-205-5p in exosomes divided from chondrogenic mesenchymal stem cells alleviated rheumatoid arthritis via regulating MDM2 in fibroblast-like synoviocytes
复制标题
从软骨间充质干细胞分离的外泌体中的 miR-205-5p 通过调节成纤维样滑膜细胞中的 MDM2 缓解类风湿关节炎
DOI：
--
复制
发表时间：
2022-03
期刊：
影响因子：
--
通讯作者：
Jing Zhou
中科院分区：
文献类型：
--
作者：
Wukai Ma;Fang Tang;Lina Xiao;Shan Han;Xueming Yao;Qiongyu Zhang;Jiayan Zhou;Yanjun Wang;Jing Zhou
目的：探讨软骨源性骨髓间充质干细胞（BMSCs）衍生外泌体在类风湿关节炎（RA）中的作用及其机制。方法：采用成软骨培养基诱导骨髓间充质干细胞成软骨。分离骨髓间充质干细胞和软骨性骨髓间充质干细胞外泌体，采用透射电子显微镜（TEM）、激光粒度分析仪和western blot对其进行表征。ELISA法检测促炎因子和基质金属蛋白酶（MMPs）的表达水平。Western bolt检测MAPK和NF-κB通路的表达。评估RA小鼠的炎症评分和病理损伤。采用荧光素酶报告基因法和RIP检测microRNA-205-5p （miR-205-5p）与小鼠双分钟2 （MDM2）之间的关系。结果：软骨源性bmscs衍生的外泌体抑制RA-FLSs的促炎细胞因子、MMPs、MAPK和NF-κB通路。miR-205-5p在软骨源性bmscs衍生的外泌体中高表达。功能上，外泌体miR-205-5p也发挥抗炎作用。此外，MDM2是miR-205-5p的直接靶点。此外，软骨源性bmscs分泌的外泌体miR-205-5p通过MDM2抑制胶原诱导关节炎（CIA）小鼠的炎症评分、关节破坏和炎症反应。结论：软骨源性bmscs衍生的外泌体miR-205-5p通过MDM2抑制RA的炎症反应、MAPK和NF-κB通路，提示外泌体miR-205-5p可能是治疗RA的潜在靶点。
Objective: To explore the role and mechanism of chondrogenic bone marrow mesenchymal stem cells (BMSCs)-derived exosomes on Rheumatoid arthritis (RA). Methods: The chondrogenesis of BMSCs was induced by chondrogenic medium. Exosomes from BMSCs and chondrogenic BMSCs were isolated and characterized by transmission electron microscope (TEM), laser particle size analyzer and western blot. ELISA was used to analyze the expression levels of pro-inflammatory cytokines and matrix metalloproteinases (MMPs). Western bolt was performed to assess MAPK and NF-κB pathways expression. The inflammation score and the pathological damage of RA mice were evaluated. Luciferase reporter assay and RIP were carried out to examine the relationship between microRNA-205-5p (miR-205-5p) and mouse double minute 2 (MDM2). Results: Chondrogenic BMSCs-derived exosomes suppressed pro-inflammatory cytokines, MMPs and MAPK and NF-κB pathways in RA-FLSs. miR-205-5p had a high expression in chondrogenic BMSCs-derived exosomes. Functionally, exosomal miR-205-5p also played the anti-inflammation effects. Besides, MDM2 was a direct target of miR-205-5p. Additionally, chondrogenic BMSCs-secreted exosomal miR-205-5p suppressed the inflammation score, joint destruction, and inflammatory response in collagen-induced arthritis (CIA) mice through MDM2. Conclusion: Chondrogenic BMSCs-derived exosomal miR-205-5p suppressed inflammatory response, MAPK and NF-κB pathways through MDM2 in RA, indicating exosomal miR-205-5p might be a potential target for RA treatment.
登录
查看更多内容
影响因子：
4
作者：
Wang, Liming;Wang, Lihua;Liu, Yongjun
通讯作者：
Liu, Yongjun
DOI：
10.11817/j.issn.1672-7347.2020.180779
发表时间：
2020-02
期刊：
Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences
影响因子：
--
作者：
Yongwen Yang;Jun Zhou;Jian Li
通讯作者：
Yongwen Yang;Jun Zhou;Jian Li
影响因子：
3.7
作者：
Bruno S;Grange C;Collino F;Deregibus MC;Cantaluppi V;Biancone L;Tetta C;Camussi G
通讯作者：
Camussi G
影响因子：
6.1
作者：
Gatti, Stefano;Bruno, Stefania;Camussi, Giovanni
通讯作者：
Camussi, Giovanni
影响因子：
4.6
作者：
Music, E.;Klein, T. J.;Doran, M. R.
通讯作者：
Doran, M. R.