| Literature DB >> 16530041 |
Luca Zacchigna1, Carmine Vecchione, Antonella Notte, Michelangelo Cordenonsi, Sirio Dupont, Silvia Maretto, Giuseppe Cifelli, Alessandra Ferrari, Angelo Maffei, Carla Fabbro, Paola Braghetta, Gennaro Marino, Giulio Selvetella, Alessandra Aretini, Claudio Colonnese, Umberto Bettarini, Giovanni Russo, Sandra Soligo, Maddalena Adorno, Paolo Bonaldo, Dino Volpin, Stefano Piccolo, Giuseppe Lembo, Giorgio M Bressan.
Abstract
TGF-beta proteins are main regulators of blood vessel development and maintenance. Here, we report an unprecedented link between TGF-beta signaling and arterial hypertension based on the analysis of mice mutant for Emilin1, a cysteine-rich secreted glycoprotein expressed in the vascular tree. Emilin1 knockout animals display increased blood pressure, increased peripheral vascular resistance, and reduced vessel size. Mechanistically, we found that Emilin1 inhibits TGF-beta signaling by binding specifically to the proTGF-beta precursor and preventing its maturation by furin convertases in the extracellular space. In support of these findings, genetic inactivation of Emilin1 causes increased TGF-beta signaling in the vascular wall. Strikingly, high blood pressure observed in Emilin1 mutants is rescued to normal levels upon inactivation of a single TGF-beta1 allele. This study highlights the importance of modulation of TGF-beta availability in the pathogenesis of hypertension.Entities:
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Year: 2006 PMID： 16530041 DOI： 10.1016/j.cell.2005.12.035
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582