NAIST 奈良先端科学技術大学院大学 バイオサイエンス領域


MicroRNA-31 and Aging: Impact on the force transfer apparatus in skeletal muscle

演題 MicroRNA-31 and Aging: Impact on the force transfer apparatus in skeletal muscle
講演者 Dr. Keith Baar(Professor, Department of Neurobiology, Physiology and Behavior, University of California Davis)
使用言語 English
日時 2017年12月19日(火曜日) 13:30~14:30
場所 大セミナー室

In very old animals, lateral force transmission in skeletal muscle is severely impaired. The dystrophin-glycoprotein (DGC) and integrin/focal adhesion complexes are important in promoting interactions between the cytoskeleton, membrane, and extracellular matrix within skeletal muscle. Thus as animals age their muscles become more prone to contraction-induced injury (Hughes et al., 2016). A specific microRNA, miR-31, binds to the 3' untranslated region (UTR) of the dystrophin mRNA and decreases its rate of translation. MiR-31 is increased >70-fold and >20-fold in skeletal muscle of mdx mice and muscular dystrophy patients respectively (Greco et al., 2009), as well as being elevated >6-fold in aged rat muscle (29-months), possibly contributing to the lower dystrophin protein in these muscles (Hughes et al., 2016). Thus we investigated miR-31 expression across the lifespan and manipulated its expression in young muscle to determine its impact on the cytoskeleton network. Male C57BL/6 mice (8 weeks-old) were subjected to in vivo electroporation of a mouse specific miR-31 plasmid (5ug) in the tibialis anterior (TA) muscle with the contralateral leg serving as a vector control (pmR-Cherry). Western blotting was performed to determine DGC complex, β-1 integrin, and α-actinin protein levels in the transfected TA muscles. Treatment comparisons were made using a paired students’ t-test. We observed a 70-fold increase in miR-31 expression levels in the transfected TA muscle compared to the contralateral control leg. The overexpression of miR-31 lead to a 22% reduction in dystrophin protein content (P=0.02) after just 7 days. Interestingly, surrounding cytoskeleton proteins such as α-sarcoglycan, sarcospan and β1-Integrin were all significantly elevated within the miR-31 transfected TA muscle. A similar adaptive response in surrounding cytoskeleton proteins has been observed in aged skeletal TA muscle (Hughes et al., 2016). Future studies will seek to investigate the functional significance of the miR-31 induced dystrophin loss on skeletal muscle.

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