title: Role of Mir-155 in Controlling HIF-1α Level and Promoting Endothelial Cell Maturation.
abstract: Stem-cell-based therapy for cardiovascular disease, especially ischemic heart disease (IHD), is a promising approach to facilitating neovascularization through the migration of stem cells to the ischemic site and their subsequent differentiation into endothelial cells (ECs). Hypoxia is a chief feature of IHD and the stem cell niche. However, whether hypoxia promotes stem cell differentiation into ECs or causes them to retain their stemness is controversial. Here, the differentiation of pluripotent stem cells (iPSCs) into endothelial cells (ECs) was induced under hypoxia. Though the angiogenic capability and angiogenesis-related autocrine/paracrine factors of the ECs were improved under hypoxia, the level of hypoxia inducible factor 1α (HIF-1α) was nonetheless found to be restricted along with the EC differentiation. The down-regulation of HIF-1α was found to have been caused by VEGF-induced microRNA-155 (miR-155). Moreover, miR-155 was also found to enhance the angiogenic capability of induced ECs by targeting E2F2 transcription factor. Hence, miR-155 not only contributes to controlling HIF-1α expression under hypoxia but also promotes angiogenesis, which is a key feature of mature ECs. Revealing the real role of hypoxia and clarifying the function of miR-155 in EC differentiation may facilitate improvement of angiogenic gene- and stem-cell-based therapies for ischemic heart disease.
authors.affiliation: Department of Cardiology, the Third Affiliated Hospital of Southern Medical University, Guangzhou, 510000, China.
authors.forename: Deguang
authors.initials: D
authors.lastname: Yang
authors.affiliation: Department of Respiration, the Third Affiliated Hospital of Southern Medical University, Guangzhou, 510000, China.
authors.forename: Jinhong
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Nursing, the Third Affiliated Hospital of Southern Medical University, Guangzhou, 510000, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Xiao
authors.affiliation: Department of Cardiology, the Third Affiliated Hospital of Southern Medical University, Guangzhou, 510000, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Central Laboratory, the First Hospital of Jilin University, Changchun, 130032, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Shi
mesh_terms: D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D015687:Cell Hypoxia; D002460:Cell Line; D050703:E2F2 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D061252:Feeder Cells; D005347:Fibroblasts / Q000166:cytology; D005786:Gene Expression Regulation; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000235:genetics; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
chemical_list: D050703:E2F2 Transcription Factor; C493761:E2F2 protein, human; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A