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Iguratimod ameliorates rheumatoid arthritis progression through regulating miR-146a mediated IRAK1 expression and TRAF6/JNK1 pathway: an in vivo and in vitro study


1, 2, 3, 4, 5, 6

 

  1. Department of Rheumatology and Immunology, Changhai Hospital, Second Military Medical University, Shanghai, China.
  2. Department of Rheumatology and Immunology, Changhai Hospital, Naval Medical University, Shanghai, China.
  3. Department of Rheumatology and Immunology, Changhai Hospital, Naval Medical University, Shanghai, China.
  4. Department of Rheumatology and Immunology, Changhai Hospital, Naval Medical University, Shanghai, China.
  5. Department of Rheumatology and Immunology, Changhai Hospital, Naval Medical University, Shanghai, China.
  6. Department of Rheumatology and Immunology, Changhai Hospital, Naval Medical University, Shanghai, China. dongbaozhao@163.com

CER13047
2021 Vol.39, N°2
PI 0289, PF 0303
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PMID: 32662411 [PubMed]

Received: 23/12/2019
Accepted : 07/04/2020
In Press: 10/07/2020
Published: 09/04/2021

Abstract

OBJECTIVES:
This study aimed to evaluate the therapeutic effect of iguratimod and its regulatory role on microRNA (miR-146a) and the downstream genes in treating rheumatoid arthritis-fibroblast-like synoviocytes (RA-FLS) and collagen-induced arthritis (CIA) rat model.
METHODS:
RA-FLS was isolated from knee synovial tissue of an active RA patient. In vitro, the effect of miR-146a mimic/inhibition on RA-FLS functions was investigated. Then the effect of Iguratimod on cell viability, proliferation, apoptosis, migration, invasion, inflammatory cytokines, miR-146a and its downstream gene/pathway in RA-FLS was evaluated. In vivo, the collagen induced arthritis (CIA) rat model was constructed, then the effects of iguratimod, miR-146a inhibition and their combination on treating CIA rat were assessed.
RESULTS:
Iguratimod treatment increased miR-146a while decreased cell proliferation, IRAK1 and TRAF6/JNK1 pathway in RA-FLS in a dose-dependent manner. Notably, iguratimod treatment repressed cell proliferation, migration, invasion, TNF-α, IL-1β, IL-6, IL-17, IRAK1 and TRAF6/JNK1 pathway in RA-FLS, while miR-146a inhibition alleviated the abovementioned effects of Iguratimod on RA-FLS. The in vivo experiments disclosed that iguratimod reduced systemic arthritis score, and decreased TNF-α, IL-1β, IL-6, IL-17, IRAK1 as well as TRAF6/JNK1 pathway, while enhanced apoptosis in synovial tissue of CIA rat model; and in miR-146a inhibition treated CIA rat model, the effect of iguratimod was diminished.
CONCLUSIONS:
Iguratimod ameliorates RA progression via regulating miR-146a mediated IRAK1 expression and TRAF6/JNK1 pathway.

Rheumatology Article