Seminar

Seminar

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

Title MicroRNA-31 and Aging: Impact on the force transfer apparatus in skeletal muscle
Lecturer Dr. Keith Baar(Professor, Department of Neurobiology, Physiology and Behavior, University of California Davis)
Language English
Date&Time 12/19/2017 (Tue) 13:30~14:30
Venue 大セミナー室
Detail

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.

Contact 細胞シグナル
塩﨑 一裕 (kaz@bs.naist.jp)

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