Your browser doesn't support javascript.
loading
The HIF1 target gene NOX2 promotes angiogenesis through urotensin-II.
Diebold, Isabel; Petry, Andreas; Sabrane, Karim; Djordjevic, Talija; Hess, John; Görlach, Agnes.
Afiliação
  • Diebold I; Experimental and Molecular Pediatric Cardiology, Dept. of Pediatric Cardiology and Congenital Heart Disease, German Heart Center Munich at the Technical University Munich, Lazarettstr. 36, 80636 Munich, Germany.
J Cell Sci ; 125(Pt 4): 956-64, 2012 Feb 15.
Article em En | MEDLINE | ID: mdl-22399808
ABSTRACT
Urotensin-II (U-II) has been considered as one of the most potent vasoactive peptides, although its physiological and pathophysiological role is still not finally resolved. Recent evidence suggests that it promotes angiogenic responses in endothelial cells, although the underlying signalling mechanisms are unclear. Reactive oxygen species derived from NADPH oxidases are major signalling molecules in the vasculature. Because NOX2 is functional in endothelial cells, we investigated the role of the NOX2-containing NADPH oxidase in U-II-induced angiogenesis and elucidated a possible contribution of hypoxia-inducible factor-1 (HIF-1), the master regulator of hypoxic angiogenesis, in the response to U-II. We found that U-II increases angiogenesis in vitro and in vivo, and these responses were prevented by antioxidants, NOX2 knockdown and in Nox2(-/-) mice. In addition, U-II-induced angiogenesis was dependent on HIF-1. Interestingly, U-II increased NOX2 transcription involving HIF-1, and chromatin immunoprecipitation confirmed NOX2 as a target gene of HIF-1. In support, NOX2 levels were greatly diminished in U-II-stimulated isolated vessels derived from mice deficient in endothelial HIF-1. Conversely, reactive oxygen species derived from NOX2 were required for U-II activation of HIF and upregulation of HIF-1. In line with this, U-II-induced upregulation of HIF-1 was absent in Nox2(-/-) vessels. Collectively, these findings identified HIF-1 and NOX2 as partners acting in concert to promote angiogenesis in response to U-II. Because U-II has been found to be elevated in cardiovascular disorders and in tumour tissues, this feed-forward mechanism could be an interesting anti-angiogenic therapeutic option in these disorders.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Urotensinas / Glicoproteínas de Membrana / Neovascularização Fisiológica / NADPH Oxidases / Fator 1 Induzível por Hipóxia Limite: Animals / Humans Idioma: En Ano de publicação: 2012 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Urotensinas / Glicoproteínas de Membrana / Neovascularização Fisiológica / NADPH Oxidases / Fator 1 Induzível por Hipóxia Limite: Animals / Humans Idioma: En Ano de publicação: 2012 Tipo de documento: Article