TY - JOUR
T1 - Loss of microRNA-23–27–24 clusters in skeletal muscle is not influential in skeletal muscle development and exercise-induced muscle adaptation
AU - Lee, Minjung
AU - Wada, Shogo
AU - Oikawa, Satoshi
AU - Suzuki, Katsuhiko
AU - Ushida, Takashi
AU - Akimoto, Takayuki
N1 - Funding Information:
This study was supported, in part, by Grants-in Aid for Young Investigators (A) (nos 18680047 and 21680049 to T.A.) and Grants-in Aid for Scientific Research (B) (nos 25282198 and 16H03239 to T.A.) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan. M.L. was supported by MEXT. S.W. and S.O. were supported by the Japan Society for the Promotion of Science.
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - MicroRNAs are small regulatory noncoding RNAs that repress gene expression at the posttranscriptional level. Previous studies have reported that the expression of miR-23, miR-27, and miR-24, driven from two miR-23–27–24 clusters, is altered by various pathophysiological conditions. However, their functions in skeletal muscle have not been clarified. To define the roles of the miR-23–27–24 clusters in skeletal muscle, we generated double-knockout (dKO) mice muscle-specifically lacking the miR-23–27–24 clusters. The dKO mice were viable and showed normal growth. The contractile and metabolic features of the muscles, represented by the expression of the myosin heavy chain and the oxidative markers PGC1-α and COX IV, were not altered in the dKO mice compared with wild-type mice. The dKO mice showed increased cross-sectional areas of the oxidative fibers. However, this dKO did not induce functional changes in the muscles. The dKO mice also showed normal adaptation to voluntary wheel running for 4 weeks, including the glycolytic-to-oxidative fiber type switch, and increases in mitochondrial markers, succinate dehydrogenase activity, and angiogenesis. In conclusion, our data demonstrate that the miR-23–27–24 clusters have subtle effects on skeletal muscle development and endurance-exercise-induced muscle adaptation.
AB - MicroRNAs are small regulatory noncoding RNAs that repress gene expression at the posttranscriptional level. Previous studies have reported that the expression of miR-23, miR-27, and miR-24, driven from two miR-23–27–24 clusters, is altered by various pathophysiological conditions. However, their functions in skeletal muscle have not been clarified. To define the roles of the miR-23–27–24 clusters in skeletal muscle, we generated double-knockout (dKO) mice muscle-specifically lacking the miR-23–27–24 clusters. The dKO mice were viable and showed normal growth. The contractile and metabolic features of the muscles, represented by the expression of the myosin heavy chain and the oxidative markers PGC1-α and COX IV, were not altered in the dKO mice compared with wild-type mice. The dKO mice showed increased cross-sectional areas of the oxidative fibers. However, this dKO did not induce functional changes in the muscles. The dKO mice also showed normal adaptation to voluntary wheel running for 4 weeks, including the glycolytic-to-oxidative fiber type switch, and increases in mitochondrial markers, succinate dehydrogenase activity, and angiogenesis. In conclusion, our data demonstrate that the miR-23–27–24 clusters have subtle effects on skeletal muscle development and endurance-exercise-induced muscle adaptation.
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U2 - 10.1038/s41598-018-37765-3
DO - 10.1038/s41598-018-37765-3
M3 - Article
C2 - 30705375
AN - SCOPUS:85060914758
VL - 9
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 1092
ER -