title: The high-mobility group I-Y transcription factor is involved in cerebral ischemia and modulates the expression of angiogenic proteins.
abstract: The present study aims to identify transcription factors (TFs) contributing to angiogenesis, a mechanism involved in giving plasticity to the brain, as potential therapeutic targets after cerebral ischemia. The promoter sequences from candidate genes involved in angiogenesis were submitted to a comparative analysis by bioinformatics software. High-mobility group I-Y protein (HMGIY) TF characterization in a rat permanent focal cerebral ischemia model was performed by quantitative real time polymerase chain reaction and Western blot for the TF expression profile study. The TF functional study was carried out using a TF-TF interaction array and gene silencing by siRNA in rat brain microvascular endothelial cells. The results showed that the promoters shared a common TF binding site for HMGIY. The expression profile analysis in ischemic rat brain showed an increase in HMGIY mRNA in the acute phase and a progressive overexpression of protein over time post-ischemia. The interaction array analysis revealed that ischemia promotes the interaction of HMGIY with TFs involved in different cerebral plasticity processes. In vitro knockdown studies showed that angiopoietin 1 and vascular endothelial growth factor expression is controlled by HMGIY and that this TF is involved in cell survival in brain endothelial cells. These findings suggest that HMGIY is a potential therapeutic target that could promote brain repair functions after stroke.
authors.affiliation: Institut d'Investigació Biomèdica de Girona (IdIBGi), Grup Cerebrovascular - Servei de Neurologia, Hospital Universitari de Girona Dr. Josep Trueta, Av. França s/n. 17007, Girona, Spain. Electronic address: su.camosbadia@gmail.com.
authors.forename: S
authors.initials: S
authors.lastname: Camós
authors.affiliation: Institut d'Investigació Biomèdica de Girona (IdIBGi), Grup Cerebrovascular - Servei de Neurologia, Hospital Universitari de Girona Dr. Josep Trueta, Av. França s/n. 17007, Girona, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Gubern
authors.affiliation: Unidad Neurovascular, Departamento de Farmacología, Facultad de Medicina, Universidad Complutense de Madrid (UCM), and Instituto de Investigación Hospital 12 de Octubre (i+12), Avenida Complutense s/n, 28040 Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Sobrado
authors.affiliation: Institut d'Investigació Biomèdica de Girona (IdIBGi), Grup Cerebrovascular - Servei de Neurologia, Hospital Universitari de Girona Dr. Josep Trueta, Av. França s/n. 17007, Girona, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Rodríguez
authors.affiliation: Unidad Neurovascular, Departamento de Farmacología, Facultad de Medicina, Universidad Complutense de Madrid (UCM), and Instituto de Investigación Hospital 12 de Octubre (i+12), Avenida Complutense s/n, 28040 Madrid, Spain.
authors.forename: V G
authors.initials: VG
authors.lastname: Romera
authors.affiliation: Unidad Neurovascular, Departamento de Farmacología, Facultad de Medicina, Universidad Complutense de Madrid (UCM), and Instituto de Investigación Hospital 12 de Octubre (i+12), Avenida Complutense s/n, 28040 Madrid, Spain.
authors.forename: M A
authors.initials: MA
authors.lastname: Moro
authors.affiliation: Unidad Neurovascular, Departamento de Farmacología, Facultad de Medicina, Universidad Complutense de Madrid (UCM), and Instituto de Investigación Hospital 12 de Octubre (i+12), Avenida Complutense s/n, 28040 Madrid, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Lizasoain
authors.affiliation: Institut d'Investigació Biomèdica de Girona (IdIBGi), Grup Cerebrovascular - Servei de Neurologia, Hospital Universitari de Girona Dr. Josep Trueta, Av. França s/n. 17007, Girona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Serena
authors.affiliation: Institut d'Investigació Biomèdica de Girona (IdIBGi), Grup Cerebrovascular - Servei de Neurologia, Hospital Universitari de Girona Dr. Josep Trueta, Av. França s/n. 17007, Girona, Spain. Electronic address: judithmallolas@cofgi.org.
authors.forename: J
authors.initials: J
authors.lastname: Mallolas
authors.affiliation: Institut d'Investigació Biomèdica de Girona (IdIBGi), Grup Cerebrovascular - Servei de Neurologia, Hospital Universitari de Girona Dr. Josep Trueta, Av. França s/n. 17007, Girona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Castellanos
mesh_terms: D000208:Acute Disease; D042683:Angiopoietin-1 / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000098:blood supply / Q000503:physiopathology*; D002545:Brain Ischemia / Q000503:physiopathology*; D002465:Cell Movement / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D018450:Disease Progression; D042783:Endothelial Cells / Q000502:physiology; D015870:Gene Expression / Q000502:physiology; D025741:HMGA1a Protein / Q000378:metabolism*; D008297:Male; D055806:Microvessels / Q000503:physiopathology; D009474:Neurons / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D011916:Rats, Inbred F344; D014157:Transcription Factors / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D042683:Angiopoietin-1; C467629:Angpt1 protein, rat; D012333:RNA, Messenger; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D025741:HMGA1a Protein
keywords: HMGIY; angiogenesis; brain microvascular endothelial cells; brain plasticity; cerebral ischemia; transcription factor