Xin-deficient mice display myopathy, impaired contractility, attenuated muscle repair and altered satellite cell functionality

Autor:	Dhuha Al-Sajee, Thomas J. Hawke, A. Chiang, Zacharias Orfanos, R. Wathra, Samantha K. Coleman, P.F.M. van der Ven, Irena A. Rebalka, Aliyah A. Nissar
Rok vydání:	2015
Předmět:	medicine.medical_specialty Satellite Cells Skeletal Muscle Physiology Population Biology Contractility Cardiotoxin Muscular Diseases Internal medicine medicine Animals Regeneration Myocyte Muscle Skeletal Myopathy education Cell Proliferation Mice Knockout education.field_of_study TUNEL assay Regeneration (biology) Nuclear Proteins Skeletal muscle DNA-Binding Proteins Mice Inbred C57BL medicine.anatomical_structure Endocrinology medicine.symptom Muscle Contraction
Zdroj:	Acta Physiologica. 214:248-260
ISSN:	1748-1708
DOI:	10.1111/apha.12455
Popis:	Aim 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 SCs, we studied SCs 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 SCs 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 SCs did not translate to more proliferating myoblasts, we investigated whether Xin-/- SCs displayed an exaggerated loss by apoptosis. More apoptotic SCs (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.
Databáze:	OpenAIRE
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