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微小RNA、肌肉生长抑制素与代谢率降低:冬眠动物骨骼肌萎缩抗性

MicroRNA, Myostatin, and Metabolic Rate Depression: Skeletal Muscle Atrophy Resistance in Hibernating .

作者信息

Ingelson-Filpula W Aline, Breedon Sarah A, Storey Kenneth B

机构信息

Department of Biology, Carleton University, 1125 Colonel By Drive, Ottawa, ON K1S 5B6, Canada.

Institute of Biochemistry, Carleton University, 1125 Colonel By Drive, Ottawa, ON K1S 5B6, Canada.

出版信息

Cells. 2024 Dec 16;13(24):2074. doi: 10.3390/cells13242074.

Abstract

Little brown bats () cluster in hibernacula sites over winter, in which they use metabolic rate depression (MRD) to facilitate entrance and exit of hibernation. This study used small RNA sequencing and bioinformatic analyses to identify differentially regulated microRNAs (miRNAs) and to predict their downstream effects on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) terms in the skeletal muscle of torpid as compared to euthermic controls. We observed a subset of ten miRNAs whose expression changed during hibernation, with predicted functional roles linked to cell cycle processes, downregulation of protein degradation via ubiquitin-mediated proteolysis, downregulation of signaling pathways, including MAPK, p53, mTOR, and TGFβ, and downregulation of cytoskeletal and vesicle trafficking terms. Taken together, our results indicate miRNA regulation corresponding to both widely utilized MRD survival strategies, as well as more hibernation- and tissue-specific roles in , including skeletal muscle atrophy resistance via myostatin inhibition and insulin signaling suppression.

摘要

小棕蝠在冬季聚集在冬眠场所,它们利用代谢率降低(MRD)来促进冬眠的进入和退出。本研究使用小RNA测序和生物信息学分析来鉴定差异调节的微小RNA(miRNA),并预测与正常体温对照组相比,蛰伏的小棕蝠骨骼肌中这些miRNA对基因本体论(GO)和京都基因与基因组百科全书(KEGG)术语的下游影响。我们观察到十个miRNA的一个子集,其表达在冬眠期间发生变化,预测的功能作用与细胞周期过程、通过泛素介导的蛋白水解下调蛋白质降解、下调包括丝裂原活化蛋白激酶(MAPK)、p53、雷帕霉素靶蛋白(mTOR)和转化生长因子β(TGFβ)在内的信号通路以及下调细胞骨架和囊泡运输术语有关。综上所述,我们的结果表明miRNA调节既对应广泛使用的MRD生存策略,也对应小棕蝠中更多的冬眠和组织特异性作用,包括通过抑制肌肉生长抑制素和胰岛素信号传导来抵抗骨骼肌萎缩。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5f5/11674624/d90a14da3ca2/cells-13-02074-g001.jpg

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