title: JunB regulates angiogenesis and neurovascular parallel alignment in mouse embryonic skin.
abstract: Blood vessels and nerve fibers are often closely arranged in parallel throughout the body. Therefore, neurovascular interactions have been suggested to be important for the development of vascular networks. However, the molecular mechanisms and genes regulating this process remain unclear. In the present study, we investigated the genes that are activated in endothelial cells (ECs) following interactions with neurons during vascular development. Microarray analyses of human primary microvascular ECs co-cultured with mouse primary dorsal root ganglion cells showed that JunB is strongly upregulated in ECs by neurovascular interactions. Furthermore, the forced expression of JunB in ECs stimulated a tip-like cell formation and angiogenesisin vitroand induced vascular endothelial growth factor A (VEGFA) and the pro-angiogenic integrin subunit ITGB3 expression. Moreover,in vivoknockdown of JunB in ECs from developing mouse limb skin considerably decreased the parallel alignments of blood vessels and nerve fibers. Taken together, the present data demonstrates for the first time that JunB plays an important role in the formation of embryonic vascular networks. These results contribute to the molecular understanding of neurovascular interactions during embryonic vascular development.
authors.affiliation: Department of Biochemistry, Kanazawa Medical University School of Medicine, 1-1 Daigaku, Uchinada, Kahoku-gun, Ishikawa 920-0293, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Yoshitomi
authors.affiliation: Department of Biochemistry, Kanazawa Medical University School of Medicine, 1-1 Daigaku, Uchinada, Kahoku-gun, Ishikawa 920-0293, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ikeda
authors.affiliation: Department of Biochemistry, Kanazawa Medical University School of Medicine, 1-1 Daigaku, Uchinada, Kahoku-gun, Ishikawa 920-0293, Japan.
authors.forename: Hidehito
authors.initials: H
authors.lastname: Saito
authors.affiliation: Department of Biochemistry, Kanazawa Medical University School of Medicine, 1-1 Daigaku, Uchinada, Kahoku-gun, Ishikawa 920-0293, Japan.
authors.forename: Yoshino
authors.initials: Y
authors.lastname: Yoshitake
authors.affiliation: Medical Research Institute, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Kahoku-gun, Ishikawa 920-0293, Japan.
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Ishigaki
authors.affiliation: Department of Anatomy, Kanazawa Medical University School of Medicine, 1-1 Daigaku, Uchinada, Kahoku-gun, Ishikawa 920-0293, Japan.
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Hatta
authors.affiliation: Department of Physiology, Kanazawa Medical University School of Medicine, 1-1 Daigaku, Uchinada, Kahoku-gun, Ishikawa 920-0293, Japan.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Kato
authors.affiliation: Department of Biochemistry, Kanazawa Medical University School of Medicine, 1-1 Daigaku, Uchinada, Kahoku-gun, Ishikawa 920-0293, Japan yonekura@kanazawa-med.ac.jp.
authors.forename: Hideto
authors.identifier: 0000-0002-0010-1237
authors.initials: H
authors.lastname: Yonekura
mesh_terms: D000818:Animals; D048430:Cell Shape; D003094:Collagen / Q000378:metabolism; D004622:Embryo, Mammalian / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism; D005121:Extremities / Q000196:embryology; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic; D009420:Nervous System / Q000098:blood supply* / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D015398:Signal Transduction; D012867:Skin / Q000098:blood supply / Q000196:embryology* / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C584097:JunB protein, mouse; D014157:Transcription Factors; D003094:Collagen
keywords: AP-1 transcription factor; JunB; Neurovascular interaction; Vascular remodeling