Jiajia Liu1, Jianhua Xue1, Bo Xu2, Junbo Yu1, Yuxuan Zhang3, Lili Qin4, Aixian Zhang5, Yang Yang1. 1. Department of Trauma Center, Affiliated Hospital of Nantong University Nantong, Jiangsu Province, China. 2. Department of Orthopedics, Qidong Hospital of Traditional Chinese Medicine Nantong, Jiangsu Province, China. 3. Department of Foot and Ankle Surgery, Wuxi No. 9 People's Hospital Affiliated to Soochow University Wuxi, Jiangsu Province, China. 4. Department of Endoscopic Center, Affiliated Hospital of Nantong University Nantong, Jiangsu Province, China. 5. Department of General Practice Medicine, Affiliated Hospital of Nantong University Nantong, Jiangsu Province, China.
Abstract
OBJECTIVE: Rheumatoid arthritis (RA), as a chronic autoimmune disorder, seriously threatens human health. However, no study has thoroughly illustrated the etiology of RA. The present work focused on investigating the biological functions of STAT6 and the upstream miRNAs that regulate its expression. METHODS: Synovial tissues from rheumatoid arthritis (RA) patients and normal participants were acquired. Cell viability, proliferation, apoptosis, concentrations of cytokines, miRNA and protein levels, and relative luciferase activities were detected. RESULTS: WB and qRT-PCR showed that STAT6 was obviously up-regulated in synovial tissues of RA patients as well as RA fibroblast-like synoviocytes (RA FLSs). Functionally, down-regulation of STAT6 significantly inhibited the growth of RA FLSs as indicated by EdU and CCK-8 assays. In addition, inhibition of STAT6 remarkably promoted apoptosis of RA FLSs. Besides, silence of STAT6 notably suppressed inflammatory cytokine levels, such as TNF-α, IL-6 and IL-1β. Mechanistically, STAT6 was predicted to be the direct target of and negatively regulated by miR-135a-5p. Moreover, STAT6 was involved in the regulation of miR-135a-5p on cell growth, apoptosis and inflammatory response of RA FLSs. CONCLUSION: miR-135a-5p/STAT6 is a potential novel therapeutic target for RA treatment. AJTR
OBJECTIVE: Rheumatoid arthritis (RA), as a chronic autoimmune disorder, seriously threatens human health. However, no study has thoroughly illustrated the etiology of RA. The present work focused on investigating the biological functions of STAT6 and the upstream miRNAs that regulate its expression. METHODS: Synovial tissues from rheumatoid arthritis (RA) patients and normal participants were acquired. Cell viability, proliferation, apoptosis, concentrations of cytokines, miRNA and protein levels, and relative luciferase activities were detected. RESULTS: WB and qRT-PCR showed that STAT6 was obviously up-regulated in synovial tissues of RA patients as well as RA fibroblast-like synoviocytes (RA FLSs). Functionally, down-regulation of STAT6 significantly inhibited the growth of RA FLSs as indicated by EdU and CCK-8 assays. In addition, inhibition of STAT6 remarkably promoted apoptosis of RA FLSs. Besides, silence of STAT6 notably suppressed inflammatory cytokine levels, such as TNF-α, IL-6 and IL-1β. Mechanistically, STAT6 was predicted to be the direct target of and negatively regulated by miR-135a-5p. Moreover, STAT6 was involved in the regulation of miR-135a-5p on cell growth, apoptosis and inflammatory response of RA FLSs. CONCLUSION: miR-135a-5p/STAT6 is a potential novel therapeutic target for RA treatment. AJTR
Keywords:
Fibroblast-like synoviocytes; apoptosis; microrna-135a-5p; proliferation; rheumatoid arthritis; signal transducers and activators of transcription 6
Authors: Rizi Ai; Teresina Laragione; Deepa Hammaker; David L Boyle; Andre Wildberg; Keisuke Maeshima; Emanuele Palescandolo; Vinod Krishna; David Pocalyko; John W Whitaker; Yuchen Bai; Sunil Nagpal; Kurtis E Bachman; Richard I Ainsworth; Mengchi Wang; Bo Ding; Percio S Gulko; Wei Wang; Gary S Firestein Journal: Nat Commun Date: 2018-05-15 Impact factor: 14.919