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Cell 2006 Mar 10;1245:929-42. doi: 10.1016/j.cell.2005.12.035.
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Emilin1 links TGF-beta maturation to blood pressure homeostasis.

Zacchigna L , Vecchione C , Notte A , Cordenonsi M , Dupont S , Maretto S , Cifelli G , Ferrari A , Maffei A , Fabbro C , Braghetta P , Marino G , Selvetella G , Aretini A , Colonnese C , Bettarini U , Russo G , Soligo S , Adorno M , Bonaldo P , Volpin D , Piccolo S , Lembo G , Bressan GM .

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.

PubMed ID: 16530041
Article link: Cell
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: bmp2 bmp4 emilin1 eomes fgf1 fgf4 furin mixer myod1 tbxt tgfb1 tgfbr1 vegt wnt8a

Disease Ontology terms: hypertension

Article Images: [+] show captions
References :
Raman, TGF-beta regulation by Emilin1: new links in the etiology of hypertension. 2006, Pubmed