RECK-Mediated β1-Integrin Regulation by TGF-β1 Is Critical for Wound Contraction in Mice.

Bibliographic Details
Title: RECK-Mediated β1-Integrin Regulation by TGF-β1 Is Critical for Wound Contraction in Mice.
Authors: Jaime Gutiérrez, Cristian A Droppelmann, Osvaldo Contreras, Chiaki Takahashi, Enrique Brandan
Source: PLoS ONE, Vol 10, Iss 8, p e0135005 (2015)
Publisher Information: Public Library of Science (PLoS), 2015.
Publication Year: 2015
Collection: LCC:Medicine
LCC:Science
Subject Terms: Medicine, Science
More Details: Fibroblasts are critical for wound contraction; a pivotal step in wound healing. They produce and modify the extracellular matrix (ECM) required for the proper tissue remodeling. Reversion-inducing cysteine-rich protein with Kazal motifs (RECK) is a key regulator of ECM homeostasis and turnover. However, its role in wound contraction is presently unknown. Here we describe that Transforming growth factor type β1 (TGF-β1), one of the main pro-fibrotic wound-healing promoting factors, decreases RECK expression in fibroblasts through the Smad and JNK dependent pathways. This TGF-β1 dependent downregulation of RECK occurs with the concomitant increase of β1-integrin, which is required for fibroblasts adhesion and wound contraction through the activation of focal adhesion kinase (FAK). Loss and gain RECK expression experiments performed in different types of fibroblasts indicate that RECK downregulation mediates TGF-β1 dependent β1-integrin expression. Also, reduced levels of RECK potentiate TGF-β1 effects over fibroblasts FAK-dependent contraction, without affecting its cognate signaling. The above results were confirmed on fibroblasts derived from the Reck+/- mice compared to wild type-derived fibroblasts. We observed that Reck+/- mice heal dermal wounds more efficiently than wild type mice. Our results reveal a critical role for RECK in skin wound contraction as a key mediator in the axis: TGF-β1-RECK-β1-integrin.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1932-6203
Relation: http://europepmc.org/articles/PMC4527692?pdf=render; https://doaj.org/toc/1932-6203
DOI: 10.1371/journal.pone.0135005
Access URL: https://doaj.org/article/587d7341cb35488882a979b4c55f2bca
Accession Number: edsdoj.587d7341cb35488882a979b4c55f2bca
Database: Directory of Open Access Journals
More Details
ISSN:19326203
DOI:10.1371/journal.pone.0135005
Published in:PLoS ONE
Language:English