17β-estradiol promotes angiogenesis through non-genomic activation of Smad1 signaling in endometriosis

Xinran Zhao, Zhao X, Li X, Xiaosa Li, Pei Liu, Liu P, Ping Li, Li P, Xu X, Xingyan Xu, Chen Y, Yiwen Chen, Cheng Y, Yang Cheng, Dongxing Zhu, Xiaodong Fu, Fu X
Vascular pharmacology · 2021 · vol. 142 , pp. 106932 · doi:10.1016/j.vph.2021.106932 · PMID:34763099 · W3214551539
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17β-estradiol promotes angiogenesis in endometriosis via non-genomic activation of Smad1 signaling, contributing to the disease's development.

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Abstract

17β-estradiol (E2) plays a key role in endometriosis through regulation of angiogenesis. Smad1 has been reported to be up-regulated in patients with endometriosis. However, the role of Smad1 in E2-mediated angiogenesis during the development of endometriosis remains to be determined. This study aimed to explore the role of Smad1 in E2-mediated angiogenesis during endometriosis and its underlying mechanisms. Immunofluorescence staining and Western blotting were performed to examine the expression of p-Smad1 in ectopic and control endometrium. Western blotting was used to examine activation of Smad1 signaling in NMECs, EMECs and HUVECs. Tube formation assay was performed to examine the effect of E2 on angiogenesis. Cell proliferation and migration was determined using in real-time by xCELLigence RTCA DP instrument. We found that the expression of p-Smad1 was significantly up-regulated in ectopic endometrium and ectopic intima microvascular endothelial cells. E2 non-genomically stimulated phosphorylation of Smad1 in HUVECs. c-Src and p44/42 MAPK(ERK1/2) signaling pathways are required for E2's induction on Smad1 phosphorylation. Moreover, caveolae is involved in E2-induced Smad1 phosphorylation in vascular endothelial cells. E2 promoted tube formation of vascular endothelial cells through c-Src/ERK1/2/Smad1 signaling pathway. Knockdown of Smad1 expression attenuated E2-induced proliferation and migration of HUVECs. In conclusion, E2 promotes proliferation, migration and tube formation of HUVECs through c-Src/ERK1/2/Smad1 signaling pathway. Our data shed new lights on the mechanisms through which E2 contributes to endometriosis, and may provide novel strategies to treat endometriosis.

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Condition tags

endometriosis

MeSH descriptors

Endometriosis Endometriosis Endothelial Cells Endothelial Cells Estradiol Estradiol Female Humans Neovascularization, Pathologic Signal Transduction

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

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