Dataset Information

A critical role for muscle ring finger-1 in acute lung injury-associated skeletal muscle wasting.

ABSTRACT:

Rationale

Acute lung injury (ALI) is a debilitating condition associated with severe skeletal muscle weakness that persists in humans long after lung injury has resolved. The molecular mechanisms underlying this condition are unknown.

Objectives

To identify the muscle-specific molecular mechanisms responsible for muscle wasting in a mouse model of ALI.

Methods

Changes in skeletal muscle weight, fiber size, in vivo contractile performance, and expression of mRNAs and proteins encoding muscle atrophy-associated genes for muscle ring finger-1 (MuRF1) and atrogin1 were measured. Genetic inactivation of MuRF1 or electroporation-mediated transduction of miRNA-based short hairpin RNAs targeting either MuRF1 or atrogin1 were used to identify their role in ALI-associated skeletal muscle wasting.

Measurements and main results

Mice with ALI developed profound muscle atrophy and preferential loss of muscle contractile proteins associated with reduced muscle function in vivo. Although mRNA expression of the muscle-specific ubiquitin ligases, MuRF1 and atrogin1, was increased in ALI mice, only MuRF1 protein levels were up-regulated. Consistent with these changes, suppression of MuRF1 by genetic or biochemical approaches prevented muscle fiber atrophy, whereas suppression of atrogin1 expression was without effect. Despite resolution of lung injury and down-regulation of MuRF1 and atrogin1, force generation in ALI mice remained suppressed.

Conclusions

These data show that MuRF1 is responsible for mediating muscle atrophy that occurs during the period of active lung injury in ALI mice and that, as in humans, skeletal muscle dysfunction persists despite resolution of lung injury.

SUBMITTER: Files DC

PROVIDER: S-EPMC3360571 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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Publications

A critical role for muscle ring finger-1 in acute lung injury-associated skeletal muscle wasting.

Files D Clark DC D'Alessio Franco R FR Johnston Laura F LF Kesari Priya P Aggarwal Neil R NR Garibaldi Brian T BT Mock Jason R JR Simmers Jessica L JL DeGorordo Antonio A Murdoch Jared J Willis Monte S MS Patterson Cam C Tankersley Clarke G CG Messi Maria L ML Liu Chun C Delbono Osvaldo O Furlow J David JD Bodine Sue C SC Cohn Ronald D RD King Landon S LS Crow Michael T MT

American journal of respiratory and critical care medicine 20120203 8

<h4>Rationale</h4>Acute lung injury (ALI) is a debilitating condition associated with severe skeletal muscle weakness that persists in humans long after lung injury has resolved. The molecular mechanisms underlying this condition are unknown.<h4>Objectives</h4>To identify the muscle-specific molecular mechanisms responsible for muscle wasting in a mouse model of ALI.<h4>Methods</h4>Changes in skeletal muscle weight, fiber size, in vivo contractile performance, and expression of mRNAs and protein ...[more]

PMID: 22312013

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Dataset Information

A critical role for muscle ring finger-1 in acute lung injury-associated skeletal muscle wasting.

Rationale

Objectives

Methods

Measurements and main results

Conclusions

Publications

A critical role for muscle ring finger-1 in acute lung injury-associated skeletal muscle wasting.

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