Aberrant Expression of Leptin in Human Endometriotic Stromal Cells Is Induced by Elevated Levels of Hypoxia Inducible Factor-1α

Wu MH, Meng-Hsing Wu, Meng‐Hsing Wu, Ko‐Fan Chen, Chen KF, Ko-Fan Chen, Shih-Chieh Lin, Shih‐Chieh Lin, Chun-Wun Lgu, Lgu CW, Shaw-Jenq Tsai, Shaw‐Jenq Tsai
The American journal of pathology · 2007 · vol. 170(2) , pp. 590–598 · doi:10.2353/ajpath.2007.060477 · PMID:17255327 · PMC1851850 · W2035176460
article OA: bronze CC0 ⤵ 79 in-corpus citations
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This study investigated the relationship between leptin and hypoxia in endometriosis, finding that elevated hypoxia-inducible factor-1α induces aberrant leptin expression in human endometriotic stromal cells.

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Abstract

Elevated expression of leptin in endometriotic tissue results in an increase in stromal cell proliferation and may contribute to the development of endometriosis. However, the underlying mechanism responsible for aberrant expression of leptin is not known. We hypothesize that aberrant expression of leptin in endometriotic stroma may be regulated by increased levels of hypoxia-inducible factor-1alpha (HIF-1alpha), the master transcription factor that controls gene expression in response to hypoxia. Herein we show that the mRNA and protein levels of HIF-1alpha were greater in ectopic endometriotic tissue compared with its eutopic counterpart. Exposure of eutopic endometrial stromal cells under hypoxic conditions or treated with desferrioxamine (DFO, chemical hypoxia) resulted in a time-dependent increase in leptin gene expression. A promoter activity assay demonstrated that HIF-1alpha induced leptin promoter activity after DFO treatment. Chromatin immunoprecipitation assay further demonstrated that binding of HIF-1alpha to leptin promoter was evident after DFO treatment. Finally, depletion of HIF-1alpha by short interference RNA abolished leptin expression in ectopic endometriotic stromal cells. Taken together, our data demonstrate that aberrant expression of leptin in ectopic endometriotic stromal cells is induced, at least in part, by an elevated level of HIF-1alpha in these cells, providing new insights into the etiology of endometriosis.

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Condition tags

endometriosis

MeSH descriptors

Endometriosis Endometrium Gene Expression Regulation Gene Expression Regulation Hypoxia-Inducible Factor 1, alpha Subunit Leptin Adult Cell Hypoxia Cells, Cultured Deferoxamine Deferoxamine Endometriosis Endometriosis Endometrium Female Humans Hypoxia-Inducible Factor 1, alpha Subunit Hypoxia-Inducible Factor 1, alpha Subunit Leptin Promoter Regions, Genetic

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