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Estrogen downregulates TAK1 expression in human fibroblast-like synoviocytes and in a rheumatoid arthritis model

Xi Li1, Miao Li2

  • 1Department of Sports Medicine and Joint Surgery, The People's Hospital of China Medical University, Shenyang, Liaoning 110000, P.R. China.

Experimental and Therapeutic Medicine
|August 4, 2020
PubMed

Insights

Estrogen (E2) reduces transforming growth factor β-activated kinase-1 (TAK1) in rheumatoid arthritis (RA) models. This finding suggests estrogen may be a potential therapeutic agent for RA by targeting TAK1.

Area of Science:

  • Immunology
  • Endocrinology
  • Molecular Biology

Background:

  • Transforming growth factor β-activated kinase-1 (TAK1) is implicated in rheumatoid arthritis (RA) pathogenesis.
  • Estrogen is known to influence arthritis progression, but its direct link to TAK1 in RA is unclear.

Purpose of the Study:

  • To investigate the association between estrogen and TAK1 in the context of rheumatoid arthritis.
  • To determine if estrogen affects TAK1 expression and RA development.

Main Methods:

  • TAK1 expression was analyzed in synoviocytes from RA patients, osteoarthritis patients, and healthy controls.
  • Fibroblast-like synoviocytes (FLS) were treated with 17β-estradiol (E2) to assess effects on TAK1 levels.
  • The efficacy of E2 in mitigating collagen-induced arthritis (CIA) was evaluated in vivo.

Main Results:

  • TAK1 was upregulated in synoviocytes of RA patients compared to controls.
  • E2 treatment significantly decreased TAK1 expression in cultured FLS in a dose-dependent manner.
  • E2 administration attenuated the development of CIA and reduced TAK1 expression in this model.

Conclusions:

  • Estrogen (E2) reduces TAK1 expression in both FLS and a collagen-induced arthritis model.
  • This reduction in TAK1 by E2 leads to the suppression of pathological processes in CIA.
  • Estrogen shows potential as a therapeutic agent for RA by targeting TAK1.
Keywords:
17β-estradiolcollagen-induced arthritisfibroblast-like synoviocytesrheumatoid arthritistransforming growth factor β-activated kinase-1

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