Hypoxia Promotes Ectopic Adhesion Ability of Endometrial Stromal Cells via TGF-β1/Smad Signaling in Endometriosis

Xiang Lin, Yongdong Dai, Wenzhi Xu, Xu W, Libing Shi, Shi L, Jin X, Xiaoying Jin, Chao Li, Li C, Zhou F, Feng Zhou, Yibin Pan, Pan Y, Yinli Zhang, Zhang Y, Lin X, Xiaona Lin, Zhang S, Songying Zhang
Endocrinology · 2018 · vol. 159(4) , pp. 1630–1641 · doi:10.1210/en.2017-03227 · PMID:29438550 · W2791755042
Lab / animal OA: bronze CC0 ⤵ 32 in-corpus citations
📄 Open PDF View on OpenAlex View on PubMed View at publisher
⚙ AI-generated summary by gemini-2.5-flash-lite, 2026-06-12 ⓘ

Hypoxia in endometriosis upregulates integrin expression and endometrial stromal cell adhesion through TGF-β1/Smad signaling activation, as demonstrated in patient samples and mouse models.

One-sentence paraphrase of the abstract; not a substitute for reading it. No clinical advice. How this works

Abstract

Hypoxia plays a vital role in the progression of endometriosis. Additionally, integrin-mediated aberrant adhesion is also essential for establishment of endometriotic lesions. In this study, we sought to determine the function of hypoxia in integrin-mediated adhesion of endometrial stromal cells (ESCs) in endometriosis. The expressions of adhesion molecule integrins (integrin α5, integrin αV, integrin β3, and integrin β5) were determined in 15 normal endometria and 15 paired eutopic and ectopic endometria by immunohistochemistry. Thirteen primary ESCs from patients with peritoneal endometriosis in the proliferative phase were cultured under a hypoxic (1% O2) or normoxic (21% O2) environment, and the expression levels of hypoxia-inducible factor (HIF)-1α, transforming growth factor (TGF)-β1, and integrins were detected by quantitative reverse transcription polymerase chain reaction and western blot. The alteration of integrins in endometriotic mouse models were also explored. Our results demonstrated that HIF-1α and integrins were highly expressed in ESCs of endometriotic lesions compared with ESCs of eutopic and normal endometrium. Hypoxia treatment significantly increased ESC adhesion abilities and integrin expression, which were positively correlated with TGF-β1 expression. Both TGF-β1 and hypoxia enhanced ESC adhesion properties, whereas hypoxia combined with TGF-β1 receptor inhibitor inhibited ESC adhesion. Knockdown of HIF-1α attenuated TGF-β1/Smad signaling activation and integrin expression and reduced ESC adhesion. Higher expression levels of HIF-1α, TGF-β1, and integrins were detected in endometriotic cysts from mice models. Our findings provide a novel insight of endometriosis that the hypoxic microenvironment stimulates ESCs to produce excessive TGF-β1 and activates the TGF-β1/Smad signaling pathway, thus enhancing integrin expression and the adhesion ability of ESCs.

My notes (saved in your browser only)

Condition tags

endometriosis

MeSH descriptors

Cell Adhesion Endometriosis Endometrium Hypoxia Smad Proteins Stromal Cells Transforming Growth Factor beta1 Cell Adhesion Cell Adhesion Endometriosis Endometriosis Endometrium Endometrium Female Female Humans Humans Hypoxia Hypoxia Hypoxia-Inducible Factor 1, alpha Subunit

Citation neighborhood (2-hop)

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. Outer rings show 2-hop neighbours — papers reached through the immediate citers/citees. [ collapse to 1-hop ]

References (40)

Cited by (36)

Source provenance

europepmc
last seen: 2026-10-10T06:11:15.153948+00:00
openalex
last seen: 2026-06-10T17:14:06.276822+00:00
pubmed
last seen: 2026-10-08T21:21:24.040401+00:00
License: CC0 · commercial use OK