BMB Rep. 2015; 48(11): 595-596  
microRNA for determining the age-related myogenic capabilities of skeletal muscle
Kwang-Pyo Lee1,#, Yeo Jin Shin1,2,# & Ki-Sun Kwon1,2,*
1Aging Research Institute, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, 2Department of Functional Genomics, Korea University of Science and Technology, Daejeon 34113, Korea
Correspondence to: E-mail: kwonks@kribb.re.kr
Received: October 16, 2015; Published online: November 30, 2015.
© Korean Society for Biochemistry and Molecular Biology. All rights reserved.

Abstract
Skeletal muscle exhibits a loss of muscle mass and function with age. Decreased regenerative potential of muscle stem/ progenitor cells is a major underlying cause of sarcopenia. We analyzed microRNAs (miRNA) that are differentially expressed in young and old myoblasts, to identify novel intrinsic factors that play a degenerative role in aged skeletal muscle. miR-431, one of decreasing miRNAs in old myoblasts, improved the myogenic differentiation when overexpressed in old myoblast, but suppressed their myogenic capability in knockdowned young myoblasts. We found that miR-431 directly binds to 3` untranslated regions (UTR) of Smad4 mRNA, and decreases its expression. Given that SMAD4 is one of the downstream effectors of TGF-β, a well-known degenerative signaling pathway in myogenesis, the decreased miR-431 in old myoblast causes SMAD4 elevation, thus resulting in defective myogenesis. Exogenous expression of miR-431 greatly improved the muscle regeneration in the cardiotoxin-injured hindlimb muscle of old mice by reducing SMAD4 levels. Since the miR-431 seed sequence is conserved in human SMAD4 3’UTR, miR-431 regulates the myogenic capacity of human skeletal myoblasts in the same manner. Our results suggest that age-associated miR-431 is required for the maintenance of the myogenic capability in myoblasts, thus underscoring its potential as a therapeutic target to slow down muscle aging.
Keywords: Differentiation, miR-431, Muscle aging, Myoblast, SMAD4


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