Hypoxia‐inhibited DUSP2 expression promotes IL‐6/STAT3 signaling in endometriosis

Kuei‐Yang Hsiao; Ning Chang; Jia‐Ling Tsai; Shih‐Chieh Lin; Shaw‐Jenq Tsai; Meng‐Hsing Wu

doi:10.1111/aji.12690

journal article Apr 25, 2017

Hypoxia‐inhibited DUSP2 expression promotes IL‐6/STAT3 signaling in endometriosis

Kuei‐Yang Hsiao

Ning Chang

Jia‐Ling Tsai Shih‐Chieh Lin Shaw‐Jenq Tsai Meng‐Hsing Wu

American Journal of Reproductive Immunology Vol. 78 No. 4 · Wiley

View at Publisher Save 10.1111/aji.12690

Abstract

ProblemHow does hypoxia‐mediated downregulation of dual‐specificity phosphatase‐2 (DUSP2) promote the development of endometriotic lesions?Method of studyThe levels of IL‐6 and DUSP2 were assessed in eutopic stromal cells with DUSP2 knockdown or hypoxia treatment. Bromodeoxyuridine (BrdU) incorporation was applied for evaluating cell proliferation. The protein levels of DUSP2, cleaved caspase‐3, phosphorylated STAT3, and STAT3 were analyzed using immunoblot.ResultsThe genomewide analysis of cells with DUSP2 overexpression indicated IL‐6 regulates multiple pathways related to inflammation, proliferation, and apoptosis. DUSP2 overexpression significantly suppressed IL‐6 expression, while DUSP2 knockdown promoted IL‐6 expression. The hypoxia‐treated eutopic stromal cells expressed higher levels of IL‐6, recapitulating the elevated levels of IL‐6 in ectopic stromal cells. The treatment with IL‐6 elicited the phosphorylation of STAT3, mimicking the elevated levels of phosphorylated STAT3 in the ectopic stromal cells. The IL‐6‐treated eutopic stromal cells showed more BrdU incorporation and less cleaved caspase‐3, which can be reversed by STAT3 inhibitor.ConclusionHypoxia‐induced IL‐6 production in endometriotic lesions is mediated via downregulation of DUSP2, which causes aberrant activation of STAT3 signaling pathway and helps the endometriotic cells survive under the ectopic environment.

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Details

Published: Apr 25, 2017
Vol/Issue: 78(4)
License: View

Authors

K

Kuei‐Yang Hsiao

Department of Physiology College of Medicine National Cheng Kung University Tainan Taiwan

N

Ning Chang

Department of Physiology College of Medicine National Cheng Kung University Tainan Taiwan; Department of Obstetrics and Gynecology College of Medicine and Hospital National Cheng Kung University Tainan Taiwan

J

Jia‐Ling Tsai

Department of Physiology College of Medicine National Cheng Kung University Tainan Taiwan

S

Shih‐Chieh Lin

Department of Physiology College of Medicine National Cheng Kung University Tainan Taiwan

S

Shaw‐Jenq Tsai

Department of Physiology College of Medicine National Cheng Kung University Tainan Taiwan

M

Meng‐Hsing Wu

Department of Physiology College of Medicine National Cheng Kung University Tainan Taiwan; Department of Obstetrics and Gynecology College of Medicine and Hospital National Cheng Kung University Tainan Taiwan

Funding

the Ministry of Science and Technology, Taiwan Award: 103-2314-B-006-068-MY2

Cite This Article

Kuei‐Yang Hsiao, Ning Chang, Jia‐Ling Tsai, et al. (2017). Hypoxia‐inhibited DUSP2 expression promotes IL‐6/STAT3 signaling in endometriosis. American Journal of Reproductive Immunology, 78(4). https://doi.org/10.1111/aji.12690

Hypoxia‐inhibited DUSP2 expression promotes IL‐6/STAT3 signaling in endometriosis

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