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Old 05-12-2015, 05:00 AM
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rss Mechano Growth Factor - The extracellular matrix and transforming growth factor-?1: T

The extracellular matrix and transforming growth factor-?1: Tale of a strained relationship.

Matrix Biol. 2015 May 7;

Authors: Hinz B

Abstract
Physiological tissue repair aims at restoring the mechano-protective properties of the extracellular matrix. Consequently, redundant regulatory mechanisms are in place ensuring that tissue remodelling terminates once matrix homeostasis is re-established. If these mechanisms fail, stromal cells become continuously activated, accumulate excessive amounts of stiff matrix, and fibrosis develops. In this mini-review, I develop the hypothesis that the mechanical state of the extracellular matrix and the pro-fibrotic transforming growth factor (TGF)-?1 cooperate to regulate the remodelling activities of stromal cells. TGF-?1 is stored in the matrix as part of a large latent complex and can be activated by cell contractile force that is transmitted by integrins. Matrix straining and stiffening lower the threshold for TGF-?1 activation by increasing the mechanical resistance to cell pulling. Different elements of this mechanism can be pharmacologically targeted to interrupt the mechanical positive feedback loop of fibrosis, including specific integrins and matrix protein interactions.


PMID: 25960420 [PubMed - as supplied by publisher]



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