2019年3月
Hypoxia Induces Hypoxia-Inducible Factor 1α and Potential HIF-Responsive Gene Expression in Uterine Leiomyoma.
Reproductive sciences (Thousand Oaks, Calif.)
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- 巻
- 26
- 号
- 3
- 開始ページ
- 428
- 終了ページ
- 435
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1177/1933719118776793
Uterine leiomyoma is characterized by abundant extracellular matrix and broad avascular areas, both constantly resulting in hypoxia, suggesting some hypoxia-induced response function. Here, we examined whether hypoxia-inducible factor 1α (HIF-1α)- mediated hypoxic response function in uterine leiomyoma. Immunoblotting detected higher basal HIF-1α protein expression in nuclear extracts from uterine leiomyoma tissues than in those from the adjacent myometrium ( P = .0011). Immunohistochemical analysis revealed the presence of HIF-1α-positive cellular components in both leiomyoma and surrounding myometrial tissues. Hypoxia decreased HIF-1α messenger RNA (mRNA), but increased HIF-1α protein in primary culture leiomyoma smooth muscle cells, and caused translocation of HIF-1α from the cytoplasm to the nucleus. Hypoxia upregulated mRNAs of 6 potential HIF-responsive genes ( ALDOA, ENO1, LDHA, VEGFA, PFKFB3, and SLC2A1). Chromatin immunoprecipitation quantitative polymerase chain reaction revealed that hypoxia significantly increased recruitment of HIF-1α binding to putative HIF-responsive elements in the HIF-responsive genes, suggesting that the HIF transcriptional complex initiates hypoxia-induced transcription of HIF-responsive genes. These results demonstrated a HIF-1α-mediated hypoxic response in uterine leiomyoma.
- ID情報
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- DOI : 10.1177/1933719118776793
- PubMed ID : 29779471