PMID- 29549296
OWN - NLM
STAT- MEDLINE
DCOM- 20191024
LR  - 20231112
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 8
IP  - 1
DP  - 2018 Mar 16
TI  - Mechanical stretch induced transcriptomic profiles in cardiac myocytes.
PG  - 4733
LID - 10.1038/s41598-018-23042-w [doi]
LID - 4733
AB  - 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.
FAU - Rysa, Jaana
AU  - Rysa J
AUID- ORCID: 0000-0003-2205-6323
AD  - School of Pharmacy, University of Eastern Finland, Kuopio, Finland. 
      jaana.rysa@uef.fi.
AD  - Research Unit of Biomedicine, Pharmacology and Toxicology, University of Oulu, 
      Oulu, Finland. jaana.rysa@uef.fi.
FAU - Tokola, Heikki
AU  - Tokola H
AD  - Research Unit of Biomedicine, Pharmacology and Toxicology, University of Oulu, 
      Oulu, Finland.
AD  - Department of Pathology, Cancer Research and Translational Medicine Research 
      Unit, University of Oulu and Oulu University Hospital, Oulu, Finland.
FAU - Ruskoaho, Heikki
AU  - Ruskoaho H
AUID- ORCID: 0000-0001-8971-1359
AD  - Research Unit of Biomedicine, Pharmacology and Toxicology, University of Oulu, 
      Oulu, Finland.
AD  - Drug Research Program, Division of Pharmacology and Pharmacotherapy, University 
      of Helsinki, Helsinki, Finland.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180316
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - *Gene Expression Regulation
MH  - *Gene Regulatory Networks
MH  - Hypertrophy/*genetics/pathology
MH  - Male
MH  - Myocytes, Cardiac/*metabolism/pathology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - *Stress, Mechanical
MH  - *Transcriptome
PMC - PMC5856749
COIS- The authors declare no competing interests.
EDAT- 2018/03/20 06:00
MHDA- 2019/10/28 06:00
PMCR- 2018/03/16
CRDT- 2018/03/18 06:00
PHST- 2017/12/13 00:00 [received]
PHST- 2018/03/06 00:00 [accepted]
PHST- 2018/03/18 06:00 [entrez]
PHST- 2018/03/20 06:00 [pubmed]
PHST- 2019/10/28 06:00 [medline]
PHST- 2018/03/16 00:00 [pmc-release]
AID - 10.1038/s41598-018-23042-w [pii]
AID - 23042 [pii]
AID - 10.1038/s41598-018-23042-w [doi]
PST - epublish
SO  - Sci Rep. 2018 Mar 16;8(1):4733. doi: 10.1038/s41598-018-23042-w.