4.5 Review

Matrix-dependent perturbation of TGFβ signaling and disease

期刊

FEBS LETTERS
卷 586, 期 14, 页码 2003-2015

出版社

WILEY
DOI: 10.1016/j.febslet.2012.05.027

关键词

Transforming growth factor beta; Extracellular matrix; Marfan syndrome; Stiff skin syndrome; Fibrillin; Integrin

资金

  1. Howard Hughes Medical Institute Funding Source: Medline

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Transforming growth factor beta (TGF beta) is a multipotent cytokine that is sequestered in the extracellular matrix (ECM) through interactions with a number of ECM proteins. The ECM serves to concentrate latent TGF beta at sites of intended function, to influence the bioavailability and/or function of TGF beta activators, and perhaps to regulate the intrinsic performance of cell surface effectors of TGF beta signal propagation. The downstream consequences of TGF beta signaling cascades in turn provide feedback modulation of the ECM. This review covers recent examples of how genetic mutations in constituents of the ECM or TGF beta signaling cascade result in altered ECM homeostasis, cellular performance and ultimately disease, with an emphasis on emerging therapeutic strategies that seek to capitalize on this refined mechanistic understanding. (C) 2012 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.

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