| First Author | Zacchigna L | Year | 2006 |
| Journal | Cell | Volume | 124 |
| Issue | 5 | Pages | 929-42 |
| PubMed ID | 16530041 | Mgi Jnum | J:115889 |
| Mgi Id | MGI:3692357 | Doi | 10.1016/j.cell.2005.12.035 |
| Citation | Zacchigna L, et al. (2006) Emilin1 links TGF-beta maturation to blood pressure homeostasis. Cell 124(5):929-42 |
| abstractText | 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. |
