PMID- 35303795 OWN - NLM STAT- MEDLINE DCOM- 20220429 LR - 20220531 IS - 1528-3658 (Electronic) IS - 1076-1551 (Print) IS - 1076-1551 (Linking) VI - 28 IP - 1 DP - 2022 Mar 18 TI - Exosomal microRNA-140-3p from human umbilical cord mesenchymal stem cells attenuates joint injury of rats with rheumatoid arthritis by silencing SGK1. PG - 36 LID - 10.1186/s10020-022-00451-2 [doi] LID - 36 AB - OBJECTIVE: Over the years, microRNAs (miRNAs) have been involved in the pathogenesis of rheumatoid arthritis (RA). We aim to investigate the role of human umbilical cord mesenchymal stem cells (HUCMSCs)-derived exosomal miR-140-3p in RA development. METHODS: Exosomes(exo) were isolated from human umbilical cord-derived mesenchymal stem cells (HUCMSCs), and this isolation was followed by the transfer of miR-140-3p. RA rat models were constructed by collagen II adjuvant and respectively treated with HUCMSCs-exo or HUCMSCs-exo carrying miR-140-3p mimic/inhibitor, and expression of miR-140-3p and serum- and glucocorticoid-inducible kinase 1 (SGK1) was assessed. Then, RA score and inflammation scoring, fibrosis degree and apoptosis, serum inflammatory response and oxidative stress in joint tissues were determined. The RA synovial fibroblasts (RASFs) were extracted from rats and identified. Conducted with relative treatment, the migration, proliferation and apoptosis in RASFs were determined. RESULTS: MiR-140-3p was decreased while SGK1 was increased in RA rats. HUCMSCs-exo or upregulated exosomal miR-140-3p improved pathological changes and suppressed inflammation, oxidative stress and fibrosis in RA rats, and also constrained and RASF growth. Overexpression of SGK1 reversed the inhibition of RASF growth caused by overexpression of miR-140-3p. CONCLUSION: Upregulated exosomal miR-140-3p attenuated joint injury of RA rats by silencing SGK1. This research provided further understanding of the role of exosomal miR-140-3p in RA development. CI - (c) 2022. The Author(s). FAU - Huang, Yijiang AU - Huang Y AD - Department of Orthopaedic, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 109 West College Road, Wenzhou, 325000, China. AD - Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, 325000, China. FAU - Chen, Liang AU - Chen L AD - Department of Orthopaedic, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 109 West College Road, Wenzhou, 325000, China. AD - Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, 325000, China. FAU - Chen, Daosen AU - Chen D AD - Department of Orthopaedic, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 109 West College Road, Wenzhou, 325000, China. AD - Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, 325000, China. FAU - Fan, Pei AU - Fan P AD - Department of Orthopaedic, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 109 West College Road, Wenzhou, 325000, China. AD - Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, 325000, China. FAU - Yu, Huachen AU - Yu H AUID- ORCID: 0000-0003-2734-4295 AD - Department of Orthopaedic, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 109 West College Road, Wenzhou, 325000, China. Yuhuachen079@163.com. AD - Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, 325000, China. Yuhuachen079@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220318 PL - England TA - Mol Med JT - Molecular medicine (Cambridge, Mass.) JID - 9501023 RN - 0 (MIRN140 microRNA, rat) RN - 0 (MicroRNAs) RN - 0 (Mirn140 microRNA, human) SB - IM MH - Animals MH - *Arthritis, Rheumatoid/genetics/therapy MH - Cell Proliferation MH - *Exosomes MH - Fibrosis MH - Humans MH - Inflammation/pathology MH - *Mesenchymal Stem Cells MH - *MicroRNAs/genetics MH - Rats MH - Umbilical Cord/pathology PMC - PMC8932126 OTO - NOTNLM OT - Exosome OT - Joint injury OT - MicroRNA-140-3p OT - Rat OT - Rheumatoid arthritis OT - Serum-and glucocorticoid-inducible kinase 1 COIS- The authors declare no competing interests. EDAT- 2022/03/20 06:00 MHDA- 2022/04/30 06:00 PMCR- 2022/03/18 CRDT- 2022/03/19 05:25 PHST- 2021/04/08 00:00 [received] PHST- 2022/02/04 00:00 [accepted] PHST- 2022/03/19 05:25 [entrez] PHST- 2022/03/20 06:00 [pubmed] PHST- 2022/04/30 06:00 [medline] PHST- 2022/03/18 00:00 [pmc-release] AID - 10.1186/s10020-022-00451-2 [pii] AID - 451 [pii] AID - 10.1186/s10020-022-00451-2 [doi] PST - epublish SO - Mol Med. 2022 Mar 18;28(1):36. doi: 10.1186/s10020-022-00451-2.