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山鸺(Dromiciops gliroides)心脏中对蛰伏有反应的微小核糖核酸

Torpor-responsive microRNAs in the heart of the Monito del monte, Dromiciops gliroides.

作者信息

Breedon Sarah A, Varma Anchal, Quintero-Galvis Julian F, Gaitán-Espitia Juan Diego, Mejías Carlos, Nespolo Roberto F, Storey Kenneth B

机构信息

Department of Biology and Institute of Biochemistry, Carleton University, Ottawa, Ontario, Canada.

Facultad de Ciencias, Instituto de Ciencias Ambientales y Evolutivas, Universidad Austral de Chile, Valdivia, Chile.

出版信息

Biofactors. 2023 Sep-Oct;49(5):1061-1073. doi: 10.1002/biof.1976. Epub 2023 May 23.

DOI:10.1002/biof.1976
PMID:37219063
Abstract

The marsupial Monito del monte (Dromiciops gliroides) utilizes both daily and seasonal bouts of torpor to preserve energy and prolong survival during periods of cold and unpredictable food availability. Torpor involves changes in cellular metabolism, including specific changes to gene expression that is coordinated in part, by the posttranscriptional gene silencing activity of microRNAs (miRNA). Previously, differential miRNA expression has been identified in D. gliroides liver and skeletal muscle; however, miRNAs in the heart of Monito del monte remained unstudied. In this study, the expression of 82 miRNAs was assessed in the hearts of active and torpid D. gliroides, finding that 14 were significantly differentially expressed during torpor. These 14 miRNAs were then used in bioinformatic analyses to identify Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways that were predicted to be most affected by these differentially expressed miRNAs. Overexpressed miRNAs were predicted to primarily regulate glycosaminoglycan biosynthesis, along with various signaling pathways such as Phosphoinositide-3-kinase/protein kinase B and transforming growth factor-β. Similarly, signaling pathways including phosphatidylinositol and Hippo were predicted to be regulated by the underexpression of miRNAs during torpor. Together, these results suggest potential molecular adaptations that protect against irreversible tissue damage and enable continued cardiac and vascular function despite hypothermia and limited organ perfusion during torpor.

摘要

有袋动物小山猴(Dromiciops gliroides)利用每日和季节性的蛰伏来保存能量,并在寒冷且食物供应不可预测的时期延长生存期。蛰伏涉及细胞代谢的变化,包括基因表达的特定变化,这部分是由微小RNA(miRNA)的转录后基因沉默活性协调的。此前,已在小山猴的肝脏和骨骼肌中鉴定出差异miRNA表达;然而,小山猴心脏中的miRNA仍未得到研究。在本研究中,评估了活跃和蛰伏状态的小山猴心脏中82种miRNA的表达,发现有14种在蛰伏期间有显著差异表达。然后将这14种miRNA用于生物信息学分析,以鉴定京都基因与基因组百科全书(KEGG)通路,预计这些通路受这些差异表达的miRNA影响最大。预测过表达的miRNA主要调节糖胺聚糖生物合成,以及各种信号通路,如磷脂酰肌醇-3-激酶/蛋白激酶B和转化生长因子-β。同样,预计蛰伏期间miRNA表达不足会调节包括磷脂酰肌醇和Hippo在内的信号通路。这些结果共同表明了潜在的分子适应性,可防止不可逆转的组织损伤,并在蛰伏期间尽管体温过低和器官灌注受限仍能维持心脏和血管的持续功能。

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