Relugolix reduces leiomyoma extracellular matrix production via the transforming growth factor-beta pathway

F&S science Pub Date : 2025-05-01 DOI:10.1016/j.xfss.2024.12.004

Adina Schwartz M.D. , Minnie Malik Ph.D. , Paul Driggers Ph.D. , William H. Catherino M.D., Ph.D.

{"title":"Relugolix reduces leiomyoma extracellular matrix production via the transforming growth factor-beta pathway","authors":"Adina Schwartz M.D. , Minnie Malik Ph.D. , Paul Driggers Ph.D. , William H. Catherino M.D., Ph.D.","doi":"10.1016/j.xfss.2024.12.004","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><div>To determine if the oral gonadotropin-releasing hormone antagonist relugolix affects leiomyoma extracellular matrix production through the transforming growth factor-beta (TGF-β) pathway.</div></div><div><h3>Design</h3><div>Laboratory study.</div></div><div><h3>Subjects</h3><div>None.</div></div><div><h3>Exposure</h3><div>Exposure of human leiomyoma cells to TGF-β and/or relugolix.</div></div><div><h3>Main Outcome Measures</h3><div>Production of TGF-β, pSMAD2/3, SMAD2/3, collagen 1A1 (COL1A1), fibronectin (FN1), and versican (VCAN) in treated and untreated leiomyoma cells.</div></div><div><h3>Results</h3><div>Transforming growth factor-beta 3 production decreased at 24 hours with relugolix 10 nM (0.80 ± 0.09-fold) and 100 nM (0.86 ± 0.06-fold) and at 48 hours with relugolix 1 nM (0.86 ± 0.05-fold) and 100 nM (0.86 ± 0.06-fold). pSMAD2/3 production decreased at 24 hours with relugolix 1 nM (0.71 ± 0.01-fold), 10 nM (0.68 ± 0.01-fold), and 100 nM (0.41 ± 0.10-fold). Compared with relugolix treatment alone at the same concentration, combination treatment at 24 hours resulted in significantly increased COL1A1, FN1, and VCAN production with relugolix 1 nM, 10 nM, and 100 nM. At 48 hours, combination treatment resulted in significantly increased COL1A1, FN1, and VCAN production with relugolix 10 nM and 100 nM.</div></div><div><h3>Conclusion</h3><div>Relugolix regulated leiomyoma size by decreasing COL1A1, FN1, and VCAN production. This effect is at least partly through the TGF-β pathway.</div></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"6 2","pages":"Pages 213-220"},"PeriodicalIF":0.0000,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"F&S science","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2666335X24000843","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}

引用次数: 0

Abstract

Objective

To determine if the oral gonadotropin-releasing hormone antagonist relugolix affects leiomyoma extracellular matrix production through the transforming growth factor-beta (TGF-β) pathway.

Design

Laboratory study.

Subjects

None.

Exposure

Exposure of human leiomyoma cells to TGF-β and/or relugolix.

Main Outcome Measures

Production of TGF-β, pSMAD2/3, SMAD2/3, collagen 1A1 (COL1A1), fibronectin (FN1), and versican (VCAN) in treated and untreated leiomyoma cells.

Results

Transforming growth factor-beta 3 production decreased at 24 hours with relugolix 10 nM (0.80 ± 0.09-fold) and 100 nM (0.86 ± 0.06-fold) and at 48 hours with relugolix 1 nM (0.86 ± 0.05-fold) and 100 nM (0.86 ± 0.06-fold). pSMAD2/3 production decreased at 24 hours with relugolix 1 nM (0.71 ± 0.01-fold), 10 nM (0.68 ± 0.01-fold), and 100 nM (0.41 ± 0.10-fold). Compared with relugolix treatment alone at the same concentration, combination treatment at 24 hours resulted in significantly increased COL1A1, FN1, and VCAN production with relugolix 1 nM, 10 nM, and 100 nM. At 48 hours, combination treatment resulted in significantly increased COL1A1, FN1, and VCAN production with relugolix 10 nM and 100 nM.

Conclusion

Relugolix regulated leiomyoma size by decreasing COL1A1, FN1, and VCAN production. This effect is at least partly through the TGF-β pathway.

查看原文本刊更多论文

乐可利通过 TGF β 途径减少子宫肌瘤细胞外基质的生成。

目的：确定口服GnRH拮抗剂relugolix是否通过TGF β途径影响平滑肌瘤细胞外基质的生成。主要观察指标：治疗和未治疗的平滑肌瘤细胞中TGF β、pSMAD2/3、SMAD2/3、COL1A1、FN1和VCAN的产生结果：在10nM（0.80 + 0.09倍，p0.04）和100nM（0.86 + 0.06倍，p0.03）和1nM（0.86 + 0.05倍，p0.01）和100nM（0.86 + 0.06倍，p0.04）时，relugolix治疗24小时TGF β3的产生减少。relugolix 1nM（0.71 + 0.01倍，p0.002）、10nM（0.68 + 0.01倍，p0.001）和100nM（0.41 + 0.10倍，p0.004）治疗24h后pSMAD2/3降低。与相同浓度的relugolix单独处理相比，在24小时联合处理时，relugolix 1nM、10nM和100nM的COL1A1、FN1和VCAN产量显著增加。在48小时时，10nM和100nM的relugolix联合处理显著增加COL1A1、FN1和VCAN的产生。结论：Relugolix通过降低COL1A1、FN1和VCAN的生成来调节平滑肌瘤的大小。这种作用至少部分是通过TGF β途径实现的。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊