title: Homeobox D1 regulates angiogenic functions of endothelial cells via integrin β1 expression.
abstract: Homeobox (HOX) family genes, major transcription factors for embryonic development, have been also implicated in vascular development and angiogenesis, particularly with regulation of genes involved in cell-cell or cell-extracellular matrix (ECM) interactions. However, the cellular and molecular functions of HOXD1 in endothelial cells (ECs) are yet to be explored. We here report that HOXD1 is prominently expressed in human ECs and regulates angiogenic activities. Knockdown of HOXD1 in ECs resulted in significant inhibition of migration and adhesion as well as tube like structure formation. These effects were correlated with the reduced expression of integrin β1 (ITGB1), an important signaling component of angiogenesis. Consistently, ITGB1 promoter activity was decreased by HOXD1 knockdown in ECs. Furthermore, we identified the putative HOXD1-binding sites in the promoter region of ITGB1. Together, these findings suggest that HOXD1 plays a significant role in EC functions by regulating the expression of ITGB1.
authors.affiliation: College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea. happyojin@gmail.com
authors.forename: Hyojin
authors.initials: H
authors.lastname: Park
authors.forename: Hyun-Jung
authors.initials: HJ
authors.lastname: Choi
authors.forename: Jihye
authors.initials: J
authors.lastname: Kim
authors.forename: Minhyung
authors.initials: M
authors.lastname: Kim
authors.forename: Seung-Sik
authors.initials: SS
authors.lastname: Rho
authors.forename: Daehee
authors.initials: D
authors.lastname: Hwang
authors.forename: Young-Myeong
authors.initials: YM
authors.lastname: Kim
authors.forename: Young-Guen
authors.initials: YG
authors.lastname: Kwon
mesh_terms: D001665:Binding Sites; D002448:Cell Adhesion / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism / Q000502:physiology*; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics*; D018919:Neovascularization, Physiologic / Q000235:genetics*; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D018398:Homeodomain Proteins; D019012:Integrin beta1; D014157:Transcription Factors; C072064:HOXD10 protein, human