Transforming growth factor beta1 from endometriomas promotes fibrosis in surrounding ovarian tissues via Smad2/3 signaling†

Li Bing Shi, Shi Li, Feng Zhou, Hai Yan Zhu, Hai Zhu, Dong Huang, Xiao Ying Jin, Chao Li, Yongdong Dai, Yi Bin Pan, Yi Pan, Song Ying Zhang
Biology of reproduction · 2017 · vol. 97(6) , pp. 873–882 · doi:10.1093/biolre/iox140 · PMID:29136085 · W2767556136
article OA: closed CC0 ⤵ 51 in-corpus citations
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Endometriotic cells in endometriomas synthesize TGF-beta1, which promotes fibrosis in surrounding ovarian tissues through the Smad2/3 signaling pathway, causing adhesion.

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Abstract

To elucidate whether the endometriotic cells of endometriomas synthesize transforming growth factor beta1 (TGF-beta1) and understand how it affects surrounding ovarian tissue. We collected biopsies of the cystic walls from 42 endometriomas and 29 mature teratomas and compared mRNA and protein expression of fibrosis-related factors between the cystic walls. Then we detected TGFB1 mRNA synthesis in endometriomas, and tested TGF-beta1 fibrotic effect in vitro. Moreover, we verified the expression of Smad2/3 signaling components in the endometriotic cystic wall in order to understand whether TGF-beta1/Smad signaling is involved in fibrosis formation of the tissue surrounding endometriomas. The cystic walls from endometriomas demonstrated severe adhesion to ovarian tissue and obvious fibrosis compared with the mature teratomas, which was proven by the increased mRNA expression of fibrotic markers. Additionally, TGFB1 was obviously expressed in the endometriotic cystic wall, and total TGFB1 protein was significantly higher in the cystic walls of endometriomas than mature teratomas. Interestingly, TGFB1 mRNA was confirmed to be specifically synthesized in the endometriotic loci through fluorescence in situ hybridization. Cultured endometriomas derived stromal cells showed obvious fibrosis after exposed to TGF-beta1. Furthermore, components of the TGF-beta1/Smad pathway such as Smad2, Smad3, Smad4, and their phosphorylated forms were also expressed in the same location as TGF-beta1, TGF-beta receptor1, and fibrotic factors expressed in the endometriotic cystic walls. In summary, endometriotic cells of endometriomas synthesize TGF-beta1 leading to fibrosis and adhesion to ovarian tissues, and TGF-beta1/Smad signaling pathway is involved in this pathological process.

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Condition tags

mesh:D004715

MeSH descriptors

Endometriosis Ovary Smad2 Protein Smad3 Protein Transforming Growth Factor beta1 Adult Endometriosis Female Fibrosis Humans Middle Aged Ovary RNA, Messenger RNA, Messenger Signal Transduction Smad2 Protein Smad3 Protein Stromal Cells Stromal Cells Transforming Growth Factor beta1

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