Emilin1 links TGF-beta maturation to blood pressure homeostasis

Cell. 2006 Mar 10;124(5):929-42. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arteries / cytology
  • Arteries / metabolism
  • Blood Pressure / physiology*
  • Furin / metabolism
  • Gene Dosage
  • Genes, Reporter
  • Homeostasis*
  • Humans
  • Hypertension / etiology
  • Hypertension / metabolism
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Nodal Protein
  • Phenotype
  • Protein Precursors / metabolism
  • Protein Structure, Tertiary
  • Receptors, Transforming Growth Factor beta / genetics
  • Receptors, Transforming Growth Factor beta / metabolism
  • Signal Transduction / physiology*
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism*
  • Xenopus laevis / embryology
  • Xenopus laevis / genetics
  • Xenopus laevis / metabolism


  • Membrane Glycoproteins
  • NODAL protein, human
  • Nodal Protein
  • Nodal protein, mouse
  • Protein Precursors
  • Receptors, Transforming Growth Factor beta
  • Transforming Growth Factor beta
  • elastin microfibril interface located protein
  • Furin