Low STING expression promotes endometrial stromal cell invasion and migration via the STING/IRF-3/IFN-β1 pathway in eutopic endometrium of women with endometriosis

Zhen Xu, Xu Z, Zhao H, Heng Zhao, Caixin Yue, Yue C, Zhang L, Lixia Zhang, Muzi Li, Li M, Du Y, Yanbo Du, Zhang N, Na Zhang, Yan L, Lei Yan
Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology · 2022 · vol. 38(12) , pp. 1129–1135 · doi:10.1080/09513590.2022.2154338 · PMID:36509095 · W4311207782
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Low STING expression in eutopic endometrium from endometriosis patients is linked to increased stromal cell invasion and migration via reduced STING/IRF-3/IFN-β1 signaling.

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Abstract

Aims: The primary aim of the current study was to elucidate the function of the stimulator of interferon genes (STING) in the eutopic endometrium of women with endometriosis. Materials and Methods: STING expression and signaling pathways were verified by western blot analysis and immunohistochemistry after si-STING treatment. Cell proliferation and invasion and migration were assessed using 5-ethynyl-2'-deoxyuridine and transwell assays, respectively. Results: Within endometriosis tissues, STING was primarily expressed in the stroma of the eutopic endometrium and glandular epithelium of the ectopic endometrium. However, STING expression was significantly lower in the eutopic endometrium of patients with endometriosis compared to controls (p < 0.05). Additionally, cell proliferation (0.2866 ± 0.01470 vs. 0.6911 ± 0.01796, ****p < 0.0001), invasion (130.0 ± 6.296 vs. 424.1 ± 22.31, ****p < 0.0001), and migration (82.93 ± 6.940 vs. 82.93 ± 6.940, ****p < 0.0001) were significantly increased in the si-STING groups. Moreover, following si-STING transfection, the expression of phosphorylated IRF-3 and TBK1 that are involved in STING/IRF3/IFNb1 signaling pathway decreased. The addition of exogenous IFN-β1 effectively increased stromal cell invasion (IFN-β1-NC vs. IFN-β1-si-STING 274.7 ± 7.767 vs. 135.7 ± 12.63, ***p < 0.0001) and migration (IFN-β1-NC and IFN-β1-si-STING 28.53 ± 3.625 vs. 28.53 ± 3.625, ***p < 0.0001) without significantly impacting cell proliferation (si-STING vs. IFN-1β-si-STING 0.6874 ± 0.02081 vs. 0.7187 ± 0.02638, p = 0.795). Conclusions: The STING signaling pathway plays an important role in endometrial stromal cell proliferation, invasion and migration associated with endometriosis.

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Condition tags

endometriosis

MeSH descriptors

Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis

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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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