2. Academic Validation
  3. Irisin mitigates rheumatoid arthritis by suppressing mitochondrial fission via inhibiting YAP-Drp1 signaling pathway

Irisin mitigates rheumatoid arthritis by suppressing mitochondrial fission via inhibiting YAP-Drp1 signaling pathway

  • Int Immunopharmacol. 2023 Dec 27:127:111443. doi: 10.1016/j.intimp.2023.111443.
Yongmei Yu 1,  Meican Ma 1,  Chunyan Li 1,  Qiujie Dang 1,  Hongwei Lei 1,  Gang Wang 2,  Jianling Su 3,  Yang Li 4
Affiliations

Affiliations

  • 1 Department of Rheumatology and Immunology, 2nd Affiliated Hospital of Harbin Medical University, Harbin 150001, PR China; National Key Laboratory of Frigid Zone Cardiovascular Diseases, The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin 150001, PR China.
  • 2 National Key Laboratory of Frigid Zone Cardiovascular Diseases, The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin 150001, PR China; Department of Cardiology, 2nd Affiliated Hospital of Harbin Medical University, Harbin 150001, PR China. Electronic address: [email protected].
  • 3 Department of Rheumatology and Immunology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510000, PR China. Electronic address: [email protected].
  • 4 Department of Rheumatology and Immunology, 2nd Affiliated Hospital of Harbin Medical University, Harbin 150001, PR China; National Key Laboratory of Frigid Zone Cardiovascular Diseases, The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin 150001, PR China; Department of Rheumatology and Immunology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510000, PR China. Electronic address: [email protected].
PMID: 38154212 DOI: 10.1016/j.intimp.2023.111443
Abstract

Background: Irisin is a hormone-like factor secreted by muscle cells and produced by cleavage of the membrane protein fibronectin type III domain protein 5 (FNDC5), which exerts anti-inflammatory and anti-proliferative effects. However, the effects and the underlying mechanisms of irisin in rheumatoid arthritis (RA) are still unclear.

Method: Collagen-induced arthritis (CIA) model was induced in DBA/1 mice and then treated with irisin. Arthritis index, paw thickness, weight, number of affected paws, serum inflammatory factors and related pathological tests were measured. RA fibroblast-like synoviocytes (RA-FLSs) were pretreated with IL-1β and irisin, and the migration, proliferation, invasion, oxidative stress and mitochondrial related function of RA-FLSs were detected.

Results: Irisin significantly improved arthritis symptoms in CIA mice, as indicated by reduced arthritis index, alleviated paw thickness, decreased the number of affected paws and inhibited release of inflammatory factors. Irisin alleviated joint destruction, FLSs proliferation and the expression of YES-associated protein (YAP) and mitochondrial dynamic related protein 1 (Drp1) in the FLSs of CIA mice. In vitro experiment, irisin inhibited the proliferation, migration and invasion of RA-FLSs and improved oxidative stress induced by IL-1β, thereby restraining the pathogenic transformation of RA-FLSs. Mechanically, irisin suppressed the nuclear translocation of YAP, in turn, could reduce the synthesis of Drp1 protein and inhibit the mitochondrial fission of RA-FLSs, which was reversed by YAP agonists. Therefore, irisin has a protective effect on RA.

Conclusion: Irisin inhibits the proliferation, migration, invasion and inflammatory response of RA-FLSs by inhibiting the YAP-Drp1 signaling pathway, which implies a potential therapeutic effect on RA.

Keywords

Fibroblast-like synoviocytes; Irisin; Mitochondrial fission; Rheumatoid arthritis; YAP/Drp1.

Figures
Products