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| Status |
Public on Sep 03, 2016 |
| Title |
Microarray skeletal muscle miR-499 overexpressing mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
This experiment was conducted to identify target genes of the microRNA-499 in skeletal muscle of transgenic mice that overexpressed miR-499.
The following abstract from the submitted manuscript describes the major findings of this work.
Coupling of mitochondrial function and skeletal muscle fiber type by a miR-499/Fnip1/AMPK circuit. Jing Liu, Xijun Liang, Danxia Zhou, Ling Lai, Tingting Fu, Yan Kong, Qian Zhou, Rick B. Vega, Min-Sheng Zhu, Daniel P. Kelly, Xiang Gao, and Zhenji Gan.
Upon adaption of skeletal muscle to physiological and pathophysiological stimuli, muscle fiber type and mitochondrial function are coordinately regulated. Recent studies have identified pathways involved in control of contractile proteins of oxidative type fibers. However, the mechanism for coupling of mitochondrial function to muscle contractile machinery during fiber type transition remains unknown. Here, we show that the expression of the genes encoding type I myosins, Myh7/Myh7b and their intronic miR-208b/miR-499 parallels mitochondrial function during fiber type transitions. Using in vivo approaches in mice, we found that miR-499 drives a PGC-1a-dependent mitochondrial oxidative metabolism program to match shifts in slow-twitch muscle fiber composition. Mechanistically, miR-499 directly targets Fnip1, a known AMP-activated protein kinase (AMPK)-interacting protein that negatively regulates AMPK, a known activator of PGC-1a. Inhibition of Fnip1 reactivated AMPK/PGC-1a signaling and mitochondrial function in myocytes. Restoration of the expression of miR-499 in the mdx mouse model of Duchenne muscular dystrophy (DMD) reduced the severity of DMD. Thus, we have identified a miR-499/Fnip1/AMPK circuit that can serve as a mechanism to couple muscle fiber type and mitochondrial function.
Keywords: muscle, contractile fiber type, mitochondrial function, microRNA, gene regulation
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| Overall design |
RNA from three wild-type (non-transgenic (NTG)) and three miR-499 overexpressing (MCK-miR-499) mice was analyzed. three replicates of each are provided.
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| Web link |
http://embomolmed.embopress.org/content/early/2016/08/09/emmm.201606372.long
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| Contributor(s) |
Gan Z, Kelly D |
| Citation(s) |
27506764 |
| Submission date |
Sep 01, 2015 |
| Last update date |
Mar 04, 2019 |
| Contact name |
Zhenji Gan |
| E-mail(s) |
ganzj@nju.edu.cn
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| Organization name |
Nanjing University
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| Department |
Model Animal Research Center of Nanjing University
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| Street address |
12 Xuefu Road
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| City |
Nanjing |
| ZIP/Postal code |
210061 |
| Country |
China |
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| Platforms (1) |
| GPL6246 |
[MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA294413 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE72581_RAW.tar |
24.7 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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