Smad3 signaling critically regulates fibroblast phenotype and function in healing myocardial infarction.

ABSTRACT:

Rationale

Cardiac fibroblasts are key effector cells in the pathogenesis of cardiac fibrosis. Transforming growth factor (TGF)-beta/Smad3 signaling is activated in the border zone of healing infarcts and induces fibrotic remodeling of the infarcted ventricle contributing to the development of diastolic dysfunction.

Objective

The present study explores the mechanisms responsible for the fibrogenic effects of Smad3 by dissecting its role in modulating cardiac fibroblast phenotype and function.

Methods and results

Smad3 null mice and corresponding wild-type controls underwent reperfused myocardial infarction protocols. Surprisingly, reduced collagen deposition in Smad3-/- infarcts was associated with increased infiltration with myofibroblasts. In vitro studies demonstrat

SUBMITTER: Dobaczewski M 

PROVIDER: S-EPMC2917472 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature