Abstract
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.
Get full access to this article
View all access options for this article.
References
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
