In:
Acta Physiologica, Wiley, Vol. 214, No. 2 ( 2015-06), p. 248-260
Abstract:
Xin is an F‐actin‐binding protein expressed during development of cardiac and skeletal muscle. We used Xin‐/‐ mice to determine the impact of Xin deficiency on different aspects of skeletal muscle health, including functionality and regeneration. Methods Xin‐/‐ skeletal muscles and their satellite cell ( SC ) population were investigated for the presence of myopathic changes by a series of histological and immunofluorescent stains on resting uninjured muscles. To further understand the effect of Xin loss on muscle health and its SC s, we studied SC s responses following cardiotoxin‐induced muscle injury. Functional data were determined using in situ muscle stimulation protocol. Results Compared to age‐matched wild‐type ( WT ), Xin‐/‐ muscles exhibited generalized myopathy and increased fatigability with a significantly decreased force recovery post‐fatiguing contractions. Muscle regeneration was attenuated in Xin‐/‐ mice. This impaired regeneration prompted an investigation into SC content and functionality. Although SC content was not different, significantly more activated SC s were present in Xin‐/‐ vs. WT muscles. Primary Xin‐/‐ myoblasts displayed significant reductions (approx. 50%) in proliferative capacity vs. WT ; a finding corroborated by significantly decreased MyoD‐positive nuclei in 3 days post‐injury Xin‐/‐ muscle vs. WT . As more activated SC s did not translate to more proliferating myoblasts, we investigated whether Xin‐/‐ SC s displayed an exaggerated loss by apoptosis. More apoptotic SC s ( TUNEL +/Pax7+) were present in Xin‐/‐ muscle vs. WT . Furthermore, more Xin‐/‐ myoblasts were expressing nuclear caspase‐3 compared to WT at 3 days post‐injury. Conclusion Xin deficiency leads to a myopathic condition characterized by increased muscle fatigability, impaired regeneration and SC dysfunction.
Type of Medium:
Online Resource
ISSN:
1748-1708
,
1748-1716
DOI:
10.1111/apha.2015.214.issue-2
Language:
English
Publisher:
Wiley
Publication Date:
2015
detail.hit.zdb_id:
2617148-X
detail.hit.zdb_id:
2219379-0
SSG:
12
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