Biological Significance of Local TGF-β Activation in Liver Diseases.

Hayashi, Hiromitsu and Sakai, Takao (2012) Biological Significance of Local TGF-β Activation in Liver Diseases. Frontiers in physiology, 3. 12-. ISSN 1664-042X, 1664-042X

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Abstract

The cytokine transforming growth factor-β (TGF-β) plays a pivotal role in a diverse range of cellular responses, including cell proliferation, apoptosis, differentiation, migration, adhesion, angiogenesis, stimulation of extracellular matrix (ECM) synthesis, and downregulation of ECM degradation. TGF-β and its receptors are ubiquitously expressed by most cell types and tissues in vivo. In intact adult tissues and organs, TGF-β is secreted in a biologically inactive (latent) form associated in a non-covalent complex with the ECM. In response to injury, local latent TGF-β complexes are converted into active TGF-β according to a tissue- and injury type-specific activation mechanism. Such a well and tightly orchestrated regulation in TGF-β activity enables an immediate, highly localized response to type-specific tissue injury. In the pathological process of liver fibrosis, TGF-β plays as a master profibrogenic cytokine in promoting activation and myofibroblastic differentiation of hepatic stellate cells, a central event in liver fibrogenesis. Continuous and/or persistent TGF-β signaling induces sustained production of ECM components and of tissue inhibitor of metalloproteinase synthesis. Therefore, the regulation of locally activated TGF-β levels is increasingly recognized as a therapeutic target for liver fibrogenesis. This review summarizes our present knowledge of the activation mechanisms and bioavailability of latent TGF-β in biological and pathological processes in the liver.

Item Type:	Article
Uncontrolled Keywords:	TGF-β, TSP-1, fibronectin, liver disease, local bioavailability, β6 integrin
Depositing User:	Symplectic Admin
Date Deposited:	19 Mar 2015 14:22
Last Modified:	22 May 2026 23:10
DOI:	10.3389/fphys.2012.00012
Related Websites:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/2008586
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