title: MicroRNA-20a negatively regulates expression of NLRP3-inflammasome by targeting TXNIP in adjuvant-induced arthritis fibroblast-like synoviocytes.
abstract: OBJECTIVE
  Rheumatoid arthritis (RA) is a heterogenic and systemic autoimmune disease characterized by synovitis and joint structural damage. However, the pathogenesis of RA is still obscure. It has been reported microRNA-20a (miRNA-20a) was significantly associated with the regulation of pro-inflammatory cytokines release in RA FLS. The purpose of this study was to explore the function and underlying mechanisms of miRNA-20a on NLRP3-inflammasome in adjuvant-induced arthritis (AA) fibroblast-like synoviocytes (FLSs) in vitro.
  
  
  METHODS
  In this study, using a combination of Western blotting, Q-PCR, and ELISA analysis, we investigated the influence and function of miRNA-20a on NLRP3-inflammasome by targeting TXNIP in AA FLSs.
  
  
  RESULTS
  In the present study, the expression of NLRP3-inflammasome was significant up-regulated in AA model in vitro. Our study indicated that silence of NLRP3 down-regulated the expression of NLRP3-inflammasome and the secretion of IL-1β and MMP-1. Moreover, over-expression of miR-20a decreased formation of NLRP3-inflammasome, including NLRP3, ASC and caspase-1, and suppressed the secretion of IL-1β and MMP-1, along with down-regulated the expressions of TXNIP in primary FLSs isolated from AA. With the combined use of prediction programs and luciferase assay, the rat TXNIP mRNA 3'UTR predicted to be targeted by miR-20a. Similarly, inhibitor TXNIP expression by TXNIP-siRNA markedly repressed formation of NLRP3-inflammasome and the secretion of IL-1β and MMP-1.
  
  
  CONCLUSIONS
  Taken together, these results indicate that miR-20a may play a pivotal role in the NLRP3-inflammasome by targeted inhibit TXNIP expression in AA FLSs.
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Meishan Road No. 81, 230032 Hefei, China; Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Medical University, Meishan Road No. 81, 230032 Hefei, China; Anhui Institute of Innovative Drugs, Meishan Road No. 81, 230032 Hefei, China.
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Li
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Meishan Road No. 81, 230032 Hefei, China; Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Medical University, Meishan Road No. 81, 230032 Hefei, China; Anhui Institute of Innovative Drugs, Meishan Road No. 81, 230032 Hefei, China.
authors.forename: Wen-Wen
authors.initials: WW
authors.lastname: Shen
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Meishan Road No. 81, 230032 Hefei, China; Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Medical University, Meishan Road No. 81, 230032 Hefei, China; Anhui Institute of Innovative Drugs, Meishan Road No. 81, 230032 Hefei, China.
authors.forename: Ying-Yin
authors.initials: YY
authors.lastname: Sun
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Meishan Road No. 81, 230032 Hefei, China; Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Medical University, Meishan Road No. 81, 230032 Hefei, China; Anhui Institute of Innovative Drugs, Meishan Road No. 81, 230032 Hefei, China.
authors.forename: Wan-Xia
authors.initials: WX
authors.lastname: Li
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Meishan Road No. 81, 230032 Hefei, China; Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Medical University, Meishan Road No. 81, 230032 Hefei, China; Anhui Institute of Innovative Drugs, Meishan Road No. 81, 230032 Hefei, China.
authors.forename: Zheng-Hao
authors.initials: ZH
authors.lastname: Sun
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Meishan Road No. 81, 230032 Hefei, China; Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Medical University, Meishan Road No. 81, 230032 Hefei, China; Anhui Institute of Innovative Drugs, Meishan Road No. 81, 230032 Hefei, China.
authors.forename: Yan-Hui
authors.initials: YH
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Meishan Road No. 81, 230032 Hefei, China; Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Medical University, Meishan Road No. 81, 230032 Hefei, China; Anhui Institute of Innovative Drugs, Meishan Road No. 81, 230032 Hefei, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Meishan Road No. 81, 230032 Hefei, China; Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Medical University, Meishan Road No. 81, 230032 Hefei, China; Anhui Institute of Innovative Drugs, Meishan Road No. 81, 230032 Hefei, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Huang
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Meishan Road No. 81, 230032 Hefei, China; Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Medical University, Meishan Road No. 81, 230032 Hefei, China; Anhui Institute of Innovative Drugs, Meishan Road No. 81, 230032 Hefei, China.
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Meng
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Meishan Road No. 81, 230032 Hefei, China; Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Medical University, Meishan Road No. 81, 230032 Hefei, China; Anhui Institute of Innovative Drugs, Meishan Road No. 81, 230032 Hefei, China. Electronic address: lijun@ahmu.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics* / Q000503:physiopathology; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics*; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D006801:Humans; D058847:Inflammasomes / Q000235:genetics; D035683:MicroRNAs / Q000378:metabolism*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000235:genetics*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D000070918:Synoviocytes / Q000166:cytology / Q000502:physiology; D015854:Up-Regulation
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D058847:Inflammasomes; D035683:MicroRNAs; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C493796:TXNIP protein, rat
keywords: MicroRNA-20a; NLRP3-inflammasome; RA; TXNIP