Chengqiang Zhang1, Lihua Fang2, Xiaoping Liu2, Tingting Nie2, Rui Li2, Luping Cui2, Jie Wang2, Yanhong Ji3. 1. Department of Pathogenic Biology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education of China, No. 76 Yanta West Road, Xi'an, Shaanxi 710061, China; Department of Rheumatology and Immunology, Shanxi People's Hospital, Taiyuan 030012, Shanxi Province, China. 2. Department of Rheumatology and Immunology, Shanxi People's Hospital, Taiyuan 030012, Shanxi Province, China. 3. Department of Pathogenic Biology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education of China, No. 76 Yanta West Road, Xi'an, Shaanxi 710061, China. Electronic address: tqqjfhmzen5@163.com.
Abstract
BACKGROUND/AIMS: Rheumatoid arthritis synovial fibroblasts (RASF) play an essential role in the pathogenesis of rheumatoid arthritis (RA). This study aimed to investigate the biological effects of miR-22 on RASFs. METHODS: RT-qPCR was used to detect the expressions of miR-22 and SIRT1 in RA synovial tissue. The results of miR-22 on the proliferation of RASF were examined by MTT assay. The effects of miR-22 on the secretion of TNF-α, IL-1β, and IL-6 in RASF were measured by ELISA. Target gene prediction and screening, and luciferase reporter assay were used to testify downstream target genes of miR-22. RT-qPCR and western blotting were used to detect the mRNA and protein expression of SIRT1. RESULTS: miR-22 was significantly decreased in RA synovial tissue, while SIRT1 was significantly increased in RA synovial tissue. Over-expression of miR-22 significantly inhibited the proliferation of RASFs and the secretions of inflammatory cytokines (TNF-α, IL-1β, and IL-6) in RASFs. SIRT1 was identified as a direct target of miR-22. Over-expression of miR-22 reduced the expression level of SIRT1 in RASFs. Over-expression of SIRT1 reversed the effect of miR-22 on the proliferation of RASFs and the secretion of inflammatory cytokines. CONCLUSION: MIR-22 was significantly down-regulated in RASF cells, which affected the secretions of inflammatory cytokines and cell proliferation by regulating SIRT1.
BACKGROUND/AIMS: Rheumatoid arthritis synovial fibroblasts (RASF) play an essential role in the pathogenesis of rheumatoid arthritis (RA). This study aimed to investigate the biological effects of miR-22 on RASFs. METHODS: RT-qPCR was used to detect the expressions of miR-22 and SIRT1 in RA synovial tissue. The results of miR-22 on the proliferation of RASF were examined by MTT assay. The effects of miR-22 on the secretion of TNF-α, IL-1β, and IL-6 in RASF were measured by ELISA. Target gene prediction and screening, and luciferase reporter assay were used to testify downstream target genes of miR-22. RT-qPCR and western blotting were used to detect the mRNA and protein expression of SIRT1. RESULTS:miR-22 was significantly decreased in RA synovial tissue, while SIRT1 was significantly increased in RA synovial tissue. Over-expression of miR-22 significantly inhibited the proliferation of RASFs and the secretions of inflammatory cytokines (TNF-α, IL-1β, and IL-6) in RASFs. SIRT1 was identified as a direct target of miR-22. Over-expression of miR-22 reduced the expression level of SIRT1 in RASFs. Over-expression of SIRT1 reversed the effect of miR-22 on the proliferation of RASFs and the secretion of inflammatory cytokines. CONCLUSION:MIR-22 was significantly down-regulated in RASF cells, which affected the secretions of inflammatory cytokines and cell proliferation by regulating SIRT1.
Authors: Joanna Wielińska; Rachel E Crossland; Piotr Łacina; Jerzy Świerkot; Bartosz Bugaj; Anne M Dickinson; Katarzyna Bogunia-Kubik Journal: Dis Markers Date: 2021-09-30 Impact factor: 3.434