Linked Life Data

20308426

Source:http://linkedlifedata.com/resource/pubmed/id/20308426

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2010-3-23
pubmed:abstractText
Skeletal muscle atrophy occurs in a variety of clinical settings, including cachexia, disuse, and denervation. Inflammatory cytokines have been shown to be mediators of cancer cachexia; however, the role of cytokines in denervation- and immobilization-induced skeletal muscle loss remains unknown. In this study, we demonstrate that a single cytokine, TNF-like weak inducer of apoptosis (TWEAK), mediates skeletal muscle atrophy that occurs under denervation conditions. Transgenic expression of TWEAK induces atrophy, fibrosis, fiber-type switching, and the degradation of muscle proteins. Importantly, genetic ablation of TWEAK decreases the loss of muscle proteins and spared fiber cross-sectional area, muscle mass, and strength after denervation. Expression of the TWEAK receptor Fn14 (fibroblast growth factor-inducible receptor 14) and not the cytokine is significantly increased in muscle upon denervation, demonstrating an unexpected inside-out signaling pathway; the receptor up-regulation allows for TWEAK activation of nuclear factor kappaB, causing an increase in the expression of the E3 ubiquitin ligase MuRF1. This study reveals a novel mediator of skeletal muscle atrophy and indicates that the TWEAK-Fn14 system is an important target for preventing skeletal muscle wasting.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1540-8140
pubmed:author
pubmed:issnType
Electronic
pubmed:day
22
pubmed:volume
188
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
833-49
pubmed:dateRevised
2010-12-17
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
The TWEAK-Fn14 system is a critical regulator of denervation-induced skeletal muscle atrophy in mice.
pubmed:affiliation
Department of Anatomical Sciences and Neurobiology, University of Louisville School of Medicine, Louisville, KY 40202, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural