Understanding the role of transforming growth factor-beta signalling in the heart: overview of studies using genetic mouse models.

Abstract

1. In the present review, we focus on the genetic mouse models for transforming growth factor (TGF)-beta signalling, which have aided our understanding on the role of the TGF-beta signalling pathway in cardiac hypertrophy/fibrosis and the molecular mechanisms involved. 2. Knockout of TGF-beta is embryonic lethal, indicating that TGF-beta signalling plays an important role in embryonic development. In order to avoid this defect, many mouse strains with cardiac-specific targeted genes in TGF-beta signalling have been developed. 3. The TGF-beta family signalling pathway includes Smad-dependent and -independent pathways. 4. Investigations using the genetic mouse models have confirmed and uncovered the involvement of the TGF-beta/TGF-beta-activated kinase 1 (TAK1) pathway in the development of cardiac hypertrophy and fibrosis. Although the downstream cascade of TAK1-induced cardiac hypertrophy remains only partially defined, recent research indicates that the TGF-beta/TAK1/p38 pathway is involved in cardiac fibrosis 5. Smad-dependent signalling may not be involved in, or may even be inhibitory for, cardiac hypertrophy.