%0 Journal Article
%T Hypoxia Induces Hypoxia
%A Guiwen Wang
%A Hiroshi Ishikawa
%A Kunizui Sone
%A Linlin Xu
%A Makio Shozu
%A Tatsuya Kobayashi
%J Reproductive Sciences
%@ 1933-7205
%D 2019
%R 10.1177/1933719118776793
%X 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 1¦Á (HIF-1¦Á)- mediated hypoxic response function in uterine leiomyoma. Immunoblotting detected higher basal HIF-1¦Á 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-1¦Á-positive cellular components in both leiomyoma and surrounding myometrial tissues. Hypoxia decreased HIF-1¦Á messenger RNA (mRNA), but increased HIF-1¦Á protein in primary culture leiomyoma smooth muscle cells, and caused translocation of HIF-1¦Á 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-1¦Á 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-1¦Á-mediated hypoxic response in uterine leiomyoma
%K uterine leiomyoma
%K hypoxia
%K hypoxia inducible factor
%K extracellular matrix
%U https://journals.sagepub.com/doi/full/10.1177/1933719118776793