University of Oulu

Rysä, J., Tokola, H., & Ruskoaho, H. (2018). Mechanical stretch induced transcriptomic profiles in cardiac myocytes. Scientific Reports, 8(1). https://doi.org/10.1038/s41598-018-23042-w

Mechanical stretch induced transcriptomic profiles in cardiac myocytes

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Author: Rysä, Jaana1,2; Tokola, Heikki2,3; Ruskoaho, Heikki4,5
Organizations: 1School of Pharmacy, University of Eastern Finland, Kuopio, Finland
2Research Unit of Biomedicine, Pharmacology and Toxicology, University of Oulu, Oulu, Finland
3Department of Pathology, Cancer Research and Translational Medicine Research Unit, University of Oulu and Oulu University Hospital, Oulu, Finland
4Research Unit of Biomedicine, Pharmacology and Toxicology, University of Oulu, Oulu, Finlan
5Drug Research Program, Division of Pharmacology and Pharmacotherapy, University of Helsinki, Helsinki, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 2.1 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2019061820892
Language: English
Published: , 2018
Publish Date: 2019-06-18
Description:

Abstract

Mechanical forces are able to activate hypertrophic growth of cardiomyocytes in the overloaded myocardium. However, the transcriptional profiles triggered by mechanical stretch in cardiac myocytes are not fully understood. Here, we performed the first genome-wide time series study of gene expression changes in stretched cultured neonatal rat ventricular myocytes (NRVM)s, resulting in 205, 579, 737, 621, and 1542 differentially expressed (>2-fold, P<0.05) genes in response to 1, 4, 12, 24, and 48 hours of cyclic mechanical stretch. We used Ingenuity Pathway Analysis to predict functional pathways and upstream regulators of differentially expressed genes in order to identify regulatory networks that may lead to mechanical stretch induced hypertrophic growth of cardiomyocytes. We also performed micro (miRNA) expression profiling of stretched NRVMs, and identified that a total of 8 and 87 miRNAs were significantly (P<0.05) altered by 1–12 and 24–48 hours of mechanical stretch, respectively. Finally, through integration of miRNA and mRNA data, we predicted the miRNAs that regulate mRNAs potentially leading to the hypertrophic growth induced by mechanical stretch. These analyses predicted nuclear factor-like 2 (Nrf2) and interferon regulatory transcription factors as well as the let-7 family of miRNAs as playing roles in the regulation of stretch-regulated genes in cardiomyocytes.

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Volume: 8
Article number: 4733
DOI: 10.1038/s41598-018-23042-w
OADOI: https://oadoi.org/10.1038/s41598-018-23042-w
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
Subjects:
Funding: This work was supported by grants from the Academy of Finland (Centre of Excellence -funding (H.R.) and grants 266661 (H.R.) and 276747 (J.R.), Sigrid Jusélius Foundation and Finnish Foundation for Cardiovascular Research.
Academy of Finland Grant Number: 266661
276747
Detailed Information: 266661 (Academy of Finland Funding decision)
276747 (Academy of Finland Funding decision)
Dataset Reference: Gene expression and miRNA profiling data are publicly available on Gene Expression Omnibus database GEO under the GEO IDs: GSE107551 (gene expression data) and GSE107380 (miRNA expression data).
  http://www.ncbi.nlm.nih.gov/geo/
Copyright information: © The Author(s) 2018. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
  https://creativecommons.org/licenses/by/4.0/