Hypoxia induces expression of COX-2 through the homeodomain transcription factor CDX1 and orphan nuclear receptor SHP in human endometrial cells.

Abstract:

:Endometriosis, the presence of ectopic endometrial tissue outside the uterine cavity, is a common disease affecting women during their reproductive years. The aim of this study was to identify the molecular mechanism of transcriptional regulation of inflammatory cyclooxygenase-2 (COX-2) gene during endometriosis by hypoxia. Hypoxia induced COX-2 expression in endometrial cells together with the induction of the orphan nuclear receptor SHP and intestinal-specific transcription factor Caudal-related transcription factor 1 (CDX1). Hypoxia-inducible factor (HIF)-1α was responsible for SHP induction mediated by a hypoxia. In addition, we observed that ectopic expression of CDX1 enhanced COX-2 gene expression in hypoxia-dependent fashion. Additionally, we evaluated that induction of CDX1 by hypoxia was mediated by SHP. Expression of COX-2, CDX1, SHP and HIF-1α mRNA in hypoxia-treated human endometrial cells were significantly higher than normal control cells. These results suggest that the SHP and CDX1 expression increased by hypoxia play an active role in inducing inflammatory COX-2 expression in the pathogenesis of endometriosis.

journal_name

Mol Hum Reprod

authors

Kim KH,Kim HY,Kim HH,Lee KS,Cheong J

doi

10.1093/molehr/gar036

subject

Has Abstract

pub_date

2011-11-01 00:00:00

pages

710-9

issue

11

eissn

1360-9947

issn

1460-2407

pii

gar036

journal_volume

17

pub_type

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