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UNDERSTANDING THE ROLE OF TRANSFORMING GROWTH FACTOR‐β SIGNALLING IN THE HEART: OVERVIEW OF STUDIES USING GENETIC MOUSE MODELS
Author(s) -
Xiao Han,
Zhang YouYi
Publication year - 2008
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2007.04876.x
Subject(s) - smad , transforming growth factor beta , transforming growth factor , fibrosis , biology , tgf beta signaling pathway , muscle hypertrophy , microbiology and biotechnology , embryonic stem cell , cardiac fibrosis , signalling , signal transduction , hedgehog signaling pathway , genetic model , cancer research , endocrinology , medicine , gene , genetics
SUMMARY1 In the present review, we focus on the genetic mouse models for transforming growth factor (TGF)‐β signalling, which have aided our understanding on the role of the TGF‐β signalling pathway in cardiac hypertrophy/fibrosis and the molecular mechanisms involved. 2 Knockout of TGF‐β is embryonic lethal, indicating that TGF‐β signalling plays an important role in embryonic development. In order to avoid this defect, many mouse strains with cardiac‐specific targeted genes in TGF‐β signalling have been developed. 3 The TGF‐β 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‐β/TGF‐β‐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‐β/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.