Biomedicines (Oct 2020)

Relaxin-2 May Suppress Endometriosis by Reducing Fibrosis, Scar Formation, and Inflammation

  • Osamu Yoshino,
  • Yosuke Ono,
  • Masako Honda,
  • Kyoko Hattori,
  • Erina Sato,
  • Takehiro Hiraoka,
  • Masami Ito,
  • Mutsumi Kobayashi,
  • Kenta Arai,
  • Hidekazu Katayama,
  • Hiroyoshi Tsuchida,
  • Kaori Yamada-Nomoto,
  • Shunsuke Iwahata,
  • Yoshiyuki Fukushi,
  • Shinichiro Wada,
  • Haruko Iwase,
  • Kaori Koga,
  • Yutaka Osuga,
  • Michio Iwaoka,
  • Nobuya Unno

DOI
https://doi.org/10.3390/biomedicines8110467
Journal volume & issue
Vol. 8, no. 11
p. 467

Abstract

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Background: Relaxin (RLX)-2, produced by the corpus luteum and placenta, is known to be potentially effective in fibrotic diseases of the heart, lungs, kidneys, and bladder; however, its effectiveness in endometriosis has not yet been investigated. In the present study, we conducted a comprehensive study on the effect of RLX-2 on endometriosis. We checked the expressions of LGR-7, a primary receptor of RLX-2, in endometriomas using immunohistochemistry. Endometriotic stromal cells (ESCs) purified from surgical specimens were used in in vitro experiments. The effects of RLX-2 on ESCs were evaluated by quantitative-PCR, ELISA, and Western blotting. Gel contraction assay was used to assess the contraction suppressive effect of RLX-2. The effect of RLX-2 was also examined in the endometriosis mouse model. LGR-7 was expressed in endometriotic lesions. In ESCs, RLX-2 increased the production of cAMP and suppressed the secretion of interleukin-8, an inflammatory cytokine, by 15% and mRNA expression of fibrosis-related molecules, plasminogen activator inhibitor-1 (PAI-1), and collagen-I by approximately 50% (p p = 0.01). RLX-2 may contribute to the control of endometriotic lesion by suppressing fibrosis, scar formation, and inflammation.

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