Transforming growth factor β and its role in heart disease (Review)

Liu,Guangwang; Ma,Chao; Yang,Huilin; Zhang,Pei-Ying

doi:10.3892/etm.2017.4246

Transforming growth factor β and its role in heart disease (Review)

Authors:
- Guangwang Liu
- Chao Ma
- Huilin Yang
- Pei-Ying Zhang
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Affiliations: Institute of Orthopedics, Soochow University, Soochow, Jiangsu 215006, P.R. China, Department of Cardiology, Xuzhou Central Hospital, The Affiliated Xuzhou Hospital of Medical College of Southeast University, Xuzhou, Jiangsu 221009, P.R. China
Published online on: March 20, 2017 https://doi.org/10.3892/etm.2017.4246
Pages: 2123-2128
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Myocardial infarction (MI) is a major form of heart disease that leads to immediate cardiomyocyte death due to ischemia and eventually fibrosis and scar formation and further dysfunction of myocardium and heart failure. Extracellular matrix (ECM) production and tissue repair is conducted by myofibroblasts, which are formed from the normal quiescent cardiac fibroblasts following transformational changes, through the active participation of transforming growth factor β (TGFβ) and its signaling pathways. TGFβ appears to be a ‘Master of all trades’, with respect to cardiac fibrosis, as it can promote cardiomyocyte apoptosis and cardiac hypertrophy. TGFβ signaling involves its binding to TGFβ receptor type II (TGFβRII), which recruits TGFβ receptor type I (TGFβRI), which are also known as activin receptor-like kinase (ALK) in five different isoforms. In canonical signaling pathways, ALK5 activates Smads 2 and 3, and ALK1 activates Smads 1 and 5. These pairs of Smads form a corresponding complex and then bind to Smad 4, to translocate into the nucleus, where transcriptional reprogramming is carried out to promote myofibroblast formation and ECM production, eventually leading to cardiac fibrosis. TGFβ levels are elevated in MI, thereby aggravating the myocardial injury further. Several microRNAs are involved in the regulation of TGFβ signaling at different steps, affecting different components. Therapeutic targeting of TGFβ signaling at ALK1-5 receptor activity level has met with limited success and extensive research is needed to develop therapies based on the components of TGFβ signaling pathway, for instance cardiac dysfunction and heart failure.

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