Focal adhesion kinase links mechanical force to skin fibrosis via inflammatory signaling View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2012-01

AUTHORS

Victor W Wong, Kristine C Rustad, Satoshi Akaishi, Michael Sorkin, Jason P Glotzbach, Michael Januszyk, Emily R Nelson, Kemal Levi, Josemaria Paterno, Ivan N Vial, Anna A Kuang, Michael T Longaker, Geoffrey C Gurtner

ABSTRACT

Exuberant fibroproliferation is a common complication after injury for reasons that are not well understood. One key component of wound repair that is often overlooked is mechanical force, which regulates cell-matrix interactions through intracellular focal adhesion components, including focal adhesion kinase (FAK). Here we report that FAK is activated after cutaneous injury and that this process is potentiated by mechanical loading. Fibroblast-specific FAK knockout mice have substantially less inflammation and fibrosis than control mice in a model of hypertrophic scar formation. We show that FAK acts through extracellular-related kinase (ERK) to mechanically trigger the secretion of monocyte chemoattractant protein-1 (MCP-1, also known as CCL2), a potent chemokine that is linked to human fibrotic disorders. Similarly, MCP-1 knockout mice form minimal scars, indicating that inflammatory chemokine pathways are a major mechanism by which FAK mechanotransduction induces fibrosis. Small-molecule inhibition of FAK blocks these effects in human cells and reduces scar formation in vivo through attenuated MCP-1 signaling and inflammatory cell recruitment. These findings collectively indicate that physical force regulates fibrosis through inflammatory FAK-ERK-MCP-1 pathways and that molecular strategies targeting FAK can effectively uncouple mechanical force from pathologic scar formation. More... »

PAGES

148

References to SciGraph publications

Journal

TITLE

Nature Medicine

ISSUE

1

VOLUME

18

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nm.2574

DOI

http://dx.doi.org/10.1038/nm.2574

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1000827651

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/22157678


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Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/nm.2574'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/nm.2574'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/nm.2574'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/nm.2574'


 

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