Emilin1 links TGF-β maturation to blood pressure homeostasis

被引：263

作者：

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

机构：

[1] Univ Padua, Dev Signaling Lab, Dept Histol Microbiol & Med Biotechnol, I-35121 Padua, Italy

[2] IRCCS, Neuromed Inst, Dept Angiocardioneurol, I-86077 Pozzilli, IS, Italy

[3] Univ Roma La Sapienza, Dept Expt Med & Pathol, I-00161 Rome, Italy

[4] Univ Padua, Mouse Genet Lab, Dept Histol Microbiol & Med Biotechnol, I-35121 Padua, Italy

来源：

CELL | 2006年 / 124卷 / 05期

关键词：

D O I：

10.1016/j.cell.2005.12.035

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 Emifin1 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-beta 1 allele. This study highlights the importance of modulation of TGF-beta availability in the pathogenesis of hypertension.

引用

页码：929 / 942

页数：14

共 22 条

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