Emilin1 links TGF-beta maturation to blood pressure homeostasis.

Zacchigna, L; Vecchione, Carmine; 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

doi:10.1016/j.cell.2005.12.035

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.

Titolo:	Emilin1 links TGF-beta maturation to blood pressure homeostasis.
Autori:	Zacchigna L VECCHIONE, Carmine 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 mostra contributor esterni nascondi contributor esterni
Data di pubblicazione:	2006
Rivista:	CELL
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.
Handle:	http://hdl.handle.net/11386/3877490
Appare nelle tipologie:	1.1.1 Articolo su rivista con DOI

File in questo prodotto:

Non ci sono file associati a questo prodotto.

Utilizza questo identificativo per citare o creare un link a questo documento:
http://hdl.handle.net/11386/3877490

Citazioni

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

UniSa - IRIS Institutional Research Information System

File in questo prodotto: