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

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

Problem: How does hypoxia-mediated downregulation of dual-specificity phosphatase-2 (DUSP2) promote the development of endometriotic lesions?. Method of study: The 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. Results: The 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. Conclusion: Hypoxia-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.

Original languageEnglish
Article numbere12690
JournalAmerican Journal of Reproductive Immunology
Volume78
Issue number4
DOIs
Publication statusPublished - 2017 Jan 1

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Reproductive Medicine
  • Obstetrics and Gynaecology

Fingerprint Dive into the research topics of 'Hypoxia-inhibited DUSP2 expression promotes IL-6/STAT3 signaling in endometriosis'. Together they form a unique fingerprint.

Cite this