Stromal regulation of vessel stability by MMP14 and TGFbeta.

ABSTRACT: Innate regulatory networks within organs maintain tissue homeostasis and facilitate rapid responses to damage. We identified a novel pathway regulating vessel stability in tissues that involves matrix metalloproteinase 14 (MMP14) and transforming growth factor beta 1 (TGFbeta(1)). Whereas plasma proteins rapidly extravasate out of vasculature in wild-type mice following acute damage, short-term treatment of mice in vivo with a broad-spectrum metalloproteinase inhibitor, neutralizing antibodies to TGFbeta(1), or an activin-like kinase 5 (ALK5) inhibitor significantly enhanced vessel leakage. By contrast, in a mouse model of age-related dermal fibrosis, where MMP14 activity and TGFbeta bioavailability are chronically elevated, or in mice that ectopically express TGFbeta in the epidermis, cut

SUBMITTER: Sounni NE 

PROVIDER: S-EPMC2860851 | biostudies-literature | 2010 May-Jun

REPOSITORIES: biostudies-literature