Cargando…
Relaxin-2 May Suppress Endometriosis by Reducing Fibrosis, Scar Formation, and Inflammation
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...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693148/ https://www.ncbi.nlm.nih.gov/pubmed/33142814 http://dx.doi.org/10.3390/biomedicines8110467 |
_version_ | 1783614676933804032 |
---|---|
author | Yoshino, Osamu Ono, Yosuke Honda, Masako Hattori, Kyoko Sato, Erina Hiraoka, Takehiro Ito, Masami Kobayashi, Mutsumi Arai, Kenta Katayama, Hidekazu Tsuchida, Hiroyoshi Yamada-Nomoto, Kaori Iwahata, Shunsuke Fukushi, Yoshiyuki Wada, Shinichiro Iwase, Haruko Koga, Kaori Osuga, Yutaka Iwaoka, Michio Unno, Nobuya |
author_facet | Yoshino, Osamu Ono, Yosuke Honda, Masako Hattori, Kyoko Sato, Erina Hiraoka, Takehiro Ito, Masami Kobayashi, Mutsumi Arai, Kenta Katayama, Hidekazu Tsuchida, Hiroyoshi Yamada-Nomoto, Kaori Iwahata, Shunsuke Fukushi, Yoshiyuki Wada, Shinichiro Iwase, Haruko Koga, Kaori Osuga, Yutaka Iwaoka, Michio Unno, Nobuya |
author_sort | Yoshino, Osamu |
collection | PubMed |
description | 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 < 0.05). In the gel contraction assay, RLX-2 significantly suppressed the contraction of ESCs, which was cancelled by removing RLX-2 from the medium or by adding H89, a Protein Kinase A (PKA) inhibitor. In ESCs stimulated with RLX-2, p38 MAPK phosphorylation was significantly suppressed. In the endometriosis mouse model, administration of RLX-2 significantly decreased the area of the endometriotic-like lesion with decreasing fibrotic component compared to non-treated control (p = 0.01). RLX-2 may contribute to the control of endometriotic lesion by suppressing fibrosis, scar formation, and inflammation. |
format | Online Article Text |
id | pubmed-7693148 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-76931482020-11-28 Relaxin-2 May Suppress Endometriosis by Reducing Fibrosis, Scar Formation, and Inflammation Yoshino, Osamu Ono, Yosuke Honda, Masako Hattori, Kyoko Sato, Erina Hiraoka, Takehiro Ito, Masami Kobayashi, Mutsumi Arai, Kenta Katayama, Hidekazu Tsuchida, Hiroyoshi Yamada-Nomoto, Kaori Iwahata, Shunsuke Fukushi, Yoshiyuki Wada, Shinichiro Iwase, Haruko Koga, Kaori Osuga, Yutaka Iwaoka, Michio Unno, Nobuya Biomedicines Article 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 < 0.05). In the gel contraction assay, RLX-2 significantly suppressed the contraction of ESCs, which was cancelled by removing RLX-2 from the medium or by adding H89, a Protein Kinase A (PKA) inhibitor. In ESCs stimulated with RLX-2, p38 MAPK phosphorylation was significantly suppressed. In the endometriosis mouse model, administration of RLX-2 significantly decreased the area of the endometriotic-like lesion with decreasing fibrotic component compared to non-treated control (p = 0.01). RLX-2 may contribute to the control of endometriotic lesion by suppressing fibrosis, scar formation, and inflammation. MDPI 2020-10-31 /pmc/articles/PMC7693148/ /pubmed/33142814 http://dx.doi.org/10.3390/biomedicines8110467 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Yoshino, Osamu Ono, Yosuke Honda, Masako Hattori, Kyoko Sato, Erina Hiraoka, Takehiro Ito, Masami Kobayashi, Mutsumi Arai, Kenta Katayama, Hidekazu Tsuchida, Hiroyoshi Yamada-Nomoto, Kaori Iwahata, Shunsuke Fukushi, Yoshiyuki Wada, Shinichiro Iwase, Haruko Koga, Kaori Osuga, Yutaka Iwaoka, Michio Unno, Nobuya Relaxin-2 May Suppress Endometriosis by Reducing Fibrosis, Scar Formation, and Inflammation |
title | Relaxin-2 May Suppress Endometriosis by Reducing Fibrosis, Scar Formation, and Inflammation |
title_full | Relaxin-2 May Suppress Endometriosis by Reducing Fibrosis, Scar Formation, and Inflammation |
title_fullStr | Relaxin-2 May Suppress Endometriosis by Reducing Fibrosis, Scar Formation, and Inflammation |
title_full_unstemmed | Relaxin-2 May Suppress Endometriosis by Reducing Fibrosis, Scar Formation, and Inflammation |
title_short | Relaxin-2 May Suppress Endometriosis by Reducing Fibrosis, Scar Formation, and Inflammation |
title_sort | relaxin-2 may suppress endometriosis by reducing fibrosis, scar formation, and inflammation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693148/ https://www.ncbi.nlm.nih.gov/pubmed/33142814 http://dx.doi.org/10.3390/biomedicines8110467 |
work_keys_str_mv | AT yoshinoosamu relaxin2maysuppressendometriosisbyreducingfibrosisscarformationandinflammation AT onoyosuke relaxin2maysuppressendometriosisbyreducingfibrosisscarformationandinflammation AT hondamasako relaxin2maysuppressendometriosisbyreducingfibrosisscarformationandinflammation AT hattorikyoko relaxin2maysuppressendometriosisbyreducingfibrosisscarformationandinflammation AT satoerina relaxin2maysuppressendometriosisbyreducingfibrosisscarformationandinflammation AT hiraokatakehiro relaxin2maysuppressendometriosisbyreducingfibrosisscarformationandinflammation AT itomasami relaxin2maysuppressendometriosisbyreducingfibrosisscarformationandinflammation AT kobayashimutsumi relaxin2maysuppressendometriosisbyreducingfibrosisscarformationandinflammation AT araikenta relaxin2maysuppressendometriosisbyreducingfibrosisscarformationandinflammation AT katayamahidekazu relaxin2maysuppressendometriosisbyreducingfibrosisscarformationandinflammation AT tsuchidahiroyoshi relaxin2maysuppressendometriosisbyreducingfibrosisscarformationandinflammation AT yamadanomotokaori relaxin2maysuppressendometriosisbyreducingfibrosisscarformationandinflammation AT iwahatashunsuke relaxin2maysuppressendometriosisbyreducingfibrosisscarformationandinflammation AT fukushiyoshiyuki relaxin2maysuppressendometriosisbyreducingfibrosisscarformationandinflammation AT wadashinichiro relaxin2maysuppressendometriosisbyreducingfibrosisscarformationandinflammation AT iwaseharuko relaxin2maysuppressendometriosisbyreducingfibrosisscarformationandinflammation AT kogakaori relaxin2maysuppressendometriosisbyreducingfibrosisscarformationandinflammation AT osugayutaka relaxin2maysuppressendometriosisbyreducingfibrosisscarformationandinflammation AT iwaokamichio relaxin2maysuppressendometriosisbyreducingfibrosisscarformationandinflammation AT unnonobuya relaxin2maysuppressendometriosisbyreducingfibrosisscarformationandinflammation |