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research article

Integrins and the activation of latent transforming growth factor beta1 - an intimate relationship

Wipff, Pierre-Jean
•
Hinz, Boris
2008
European journal of cell biology

Integrins are crucial for the ability of cells to sense mechanical perturbations and to transmit intracellular stress to their environment. We here review the more recently discovered role of integrins in activating the pleiotrophic cytokine transforming growth factor beta 1 (TGF-beta1). TGF-beta1 controls tissue homeostasis in embryonic and normal adult tissues and contributes to the development of fibrosis, cancer, autoimmune and vascular diseases when being mis-regulated. In most of these conditions, active TGF-beta1 is generated by dissociation from a large latent protein complex that sequesters latent TGF-beta1 in the extracellular matrix (ECM). Two main models are proposed how integrins contribute to latent TGF-beta1 activation: (1) In a protease-dependent mechanism, integrins alphavbeta8 and alphavbeta3 are suggested to simultaneously bind the latent TGF-beta1 complex and proteinases. This close vicinity at the cell surface improves enzymatic cleavage of the latent complex to release active TGF-beta1. (2) Integrins alphavbeta3, alphavbeta5, alphavbeta6, and alphavbeta8 appear to change the conformation of the latent TGF-beta1 complex by transmitting cell traction forces. This action requires association of the latent complex with a mechanically resistant ECM and is independent from proteolysis. Understanding that different integrins use different mechanisms to activate latent TGF-beta1 opens new possibilities to develop cell-specific therapeutic strategies for TGF-beta1-induced pathologies.

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Type
research article
DOI
10.1016/j.ejcb.2008.01.012
Web of Science ID

WOS:000259370300014

Author(s)
Wipff, Pierre-Jean
Hinz, Boris
Date Issued

2008

Publisher

Elsevier

Published in
European journal of cell biology
Volume

87

Issue

8-9

Start page

601

End page

615

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
LCB  
Available on Infoscience
March 25, 2010
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/48743
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