Abstract 206: microRNA-29b Contributes to Multiple Types of Muscle Atrophy
Objective: Skeletal muscle atrophy has been observed in a significant proportion of heart failure patients while little is known about the mechanisms underlying muscle atrophy, especially in multiple types of muscle atrophy. MicroRNAs (miRNAs, miRs) are among key participants in gene regulatory networks and their dysregulation contribute to lots of diseases. However, miRNAs responsible for multiple types of muscle atrophy are unclear.
Methods and Result: miRNAs were screened by miRNA arrays and were further verified by real-time reverse transcription polymerase chain reaction with the gastrocnemius sample from denervation -induce muscle atrophy. miR-130b, miR-212, miR-21, miR-221/222, miR-223 and miR-29b were upregulated >3 fold in gastrocnemius samples from denervation mice than that of sham group. However, only miR-29b presented a common change (upregulated >3) in other types of muscle atrophy models including dexamethasone-induced and fasting-induced muscle atrophy. Over-expression of miR-29b in gastrocnemius by intramuscular injection with agomiR-29b significantly promoted muscle atrophy, which is evidenced by the change in morphology (the diameter of myofiber was decrease by 60%) and increased atrophy-related genes including Atrogin-1 and MuRF-1 (upregulated for 1.5 folds and 1.4 folds, respectively). This in vivo data suggest that miR-29b is sufficient to induce muscle atrophy. In multiple types of muscle atrophy C2C12 cell models (dexamethasone, TNF-alpha and H2O2 induced), miR-29b was increased while inhibition of miR-29b could prevent that effects. Using TargetScan software, we found that IGF1 and PI3Ka were potential target genes for miR-29b, which was further validated by luciferase assays and western blotting. Moreover, over-expression of IGF1 or PI3Ka ameliorated muscle atrophy caused by miR-29b overexpression, indicating that IGF1 and PI3Ka are two target genes responsible for miR-29b’s pro-atrophy effects in muscle.
Conclusions: Our data indicated that via targeting IGF1 and PI3Ka. Inhibition of miR-29b might represent a novel therapy for multiple types of muscle atrophy including in heart failure.
Author Disclosures: J. Li: None. L. Cheng: None. Y. Bei: None. Q. Zhou: None. Y. Yu: None. S. Fu: None. L. Chen: None. J. Xiao: None.
- © 2015 by American Heart Association, Inc.