Understanding the role of transforming growth factor-beta signalling in the heart: overview of studies using genetic mouse models.
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.
Xiao
Han
H
Institute of Vascular Medicine, Peking University Third Hospital and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing, China.
Zhang
You-Yi
YY
D000818:Animals; D004195:Disease Models, Animal; D006321:Heart / Q000502:physiology*; D051379:Mice; D015398:Signal Transduction / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism*
D016212:Transforming Growth Factor beta