MOTS-c and Exercise Restore Cardiac Function by Activating of NRG1-ErbB Signaling in Diabetic Rats

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Abstract

Pathologic cardiac remodeling and dysfunction are the most common complications of type 2 diabetes. Physical exercise is important in inhibiting myocardial pathologic remodeling and restoring cardiac function in diabetes. The mitochondrial-derived peptide MOTS-c has exercise-like effects by improving insulin resistance, combatting hyperglycemia, and reducing lipid accumulation. We investigated the effects and transcriptomic profiling of MOTS-c and aerobic exercise on cardiac properties in a rat model of type 2 diabetes which was induced by feeding a high fat high sugar diet combined with an injection of a low dose of streptozotocin. Both aerobic exercise and MOTS-c treatment reduced abnormalities in cardiac structure and function. Transcriptomic function enrichment analysis revealed that MOTS-c had exercise-like effects on inflammation, myocardial apoptosis, angiogenesis and endothelial cell proliferation and migration, and showed that the NRG1-ErbB4 pathway might be an important component in both MOTS-c and exercise induced attenuation of cardiac dysfunction in diabetes. Moreover, our findings suggest that MOTS-c activates NRG1-ErbB4 signaling and mimics exercise-induced cardio-protection in diabetes.

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edgeR: a Bioconductor package for differential expression analysis of digital gene expression data

Mark Robinson, Davis J. McCarthy, Gordon K. Smyth (2009)

Summary: It is expected that emerging digital gene expression (DGE) technologies will overtake microarray technologies in the near future for many functional genomics applications. One of the fundamental data analysis tasks, especially for gene expression studies, involves determining whether there is evidence that counts for a transcript or exon are significantly different across experimental conditions. edgeR is a Bioconductor software package for examining differential expression of replicated count data. An overdispersed Poisson model is used to account for both biological and technical variability. Empirical Bayes methods are used to moderate the degree of overdispersion across transcripts, improving the reliability of inference. The methodology can be used even with the most minimal levels of replication, provided at least one phenotype or experimental condition is replicated. The software may have other applications beyond sequencing data, such as proteome peptide count data. Availability: The package is freely available under the LGPL licence from the Bioconductor web site (http://bioconductor.org). Contact: mrobinson@wehi.edu.au

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HISAT: a fast spliced aligner with low memory requirements.

Daehwan Kim, Ben Langmead, Steven L Salzberg (2018)

HISAT (hierarchical indexing for spliced alignment of transcripts) is a highly efficient system for aligning reads from RNA sequencing experiments. HISAT uses an indexing scheme based on the Burrows-Wheeler transform and the Ferragina-Manzini (FM) index, employing two types of indexes for alignment: a whole-genome FM index to anchor each alignment and numerous local FM indexes for very rapid extensions of these alignments. HISAT's hierarchical index for the human genome contains 48,000 local FM indexes, each representing a genomic region of ∼64,000 bp. Tests on real and simulated data sets showed that HISAT is the fastest system currently available, with equal or better accuracy than any other method. Despite its large number of indexes, HISAT requires only 4.3 gigabytes of memory. HISAT supports genomes of any size, including those larger than 4 billion bases.

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StringTie enables improved reconstruction of a transcriptome from RNA-seq reads.

Mihaela Pertea, Geo M Pertea, Corina M Antonescu … (2016)

Methods used to sequence the transcriptome often produce more than 200 million short sequences. We introduce StringTie, a computational method that applies a network flow algorithm originally developed in optimization theory, together with optional de novo assembly, to assemble these complex data sets into transcripts. When used to analyze both simulated and real data sets, StringTie produces more complete and accurate reconstructions of genes and better estimates of expression levels, compared with other leading transcript assembly programs including Cufflinks, IsoLasso, Scripture and Traph. For example, on 90 million reads from human blood, StringTie correctly assembled 10,990 transcripts, whereas the next best assembly was of 7,187 transcripts by Cufflinks, which is a 53% increase in transcripts assembled. On a simulated data set, StringTie correctly assembled 7,559 transcripts, which is 20% more than the 6,310 assembled by Cufflinks. As well as producing a more complete transcriptome assembly, StringTie runs faster on all data sets tested to date compared with other assembly software, including Cufflinks.

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Author and article information

Contributors

Shunchang Li: URI : https://loop.frontiersin.org/people/705326

Jiacheng Ma: URI : https://loop.frontiersin.org/people/1610956

Ismail Laher: URI : https://loop.frontiersin.org/people/10438

Journal

Journal ID (nlm-ta): Front Endocrinol (Lausanne)

Journal ID (iso-abbrev): Front Endocrinol (Lausanne)

Journal ID (publisher-id): Front. Endocrinol.

Title: Frontiers in Endocrinology

Publisher: Frontiers Media S.A.

ISSN (Electronic): 1664-2392

Publication date (Electronic): 17 March 2022

Publication date Collection: 2022

Volume: 13

Electronic Location Identifier: 812032

Affiliations

[1] ¹ Institute of Sports Medicine and Health, Chengdu Sport University , Chengdu, China

[2] ² Department of Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia , Vancouver, BC, Canada

Author notes

Edited by: Kisuk Min, The University of Texas at El Paso, United States

Reviewed by: Oscar Lorenzo, Health Research Institute Foundation Jimenez Diaz (IIS-FJD), Spain; Suixin Liu, Central South University, China

*Correspondence: Ismail Laher, ilaher@ 123456mail.ubc.ca

This article was submitted to Diabetes: Molecular Mechanisms, a section of the journal Frontiers in Endocrinology

Article

DOI: 10.3389/fendo.2022.812032

PMC ID: 8969227

PubMed ID: 35370955

SO-VID: 44c5997f-3999-43ae-90c3-5769ae1f38cb

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

History

Date received : 09 November 2021

Date accepted : 16 February 2022

Page count

Figures: 7, Tables: 1, Equations: 0, References: 71, Pages: 12, Words: 5104

Funding

Funded by: National Natural Science Foundation of China , doi 10.13039/501100001809;

MOTS-c and Exercise Restore Cardiac Function by Activating of NRG1-ErbB Signaling in Diabetic Rats

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Journal of the ASEAN Federation of Endocrine Societies

Most cited references 71

edgeR: a Bioconductor package for differential expression analysis of digital gene expression data

HISAT: a fast spliced aligner with low memory requirements.

StringTie enables improved reconstruction of a transcriptome from RNA-seq reads.

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