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FPR1 gene silencing suppresses cardiomyocyte apoptosis and ventricular remodeling in rats with ischemia/reperfusion injury through the inhibition of MAPK signaling pathway.

Abstract：

:Ischemia/reperfusion (I/R) injury, one of the leading health problems in the world, is defined as a cause of cardiomyocytes death. In the present study, we investigate the role of formyl peptide receptor 1 (FPR1) in cardiomyocyte apoptosis and ventricular remodeling of I/R injury rats and the underlying mechanism involving mitogen-activated protein kinase (MAPK) signaling pathway. The important differentially expressed genes (DEGs) in I/R injury were screened out and downstream pathways affected by DEGs were predicted. We grouped 90 rats into sham, I/R, NC siRNA, FRP1 siRNA, empty vector, and FRP1 vector groups and established a model of I/R injury in rats. CVF value, myocardial infarct areas and positive expression rate of FPR1 and MAPK were detected. Levels of FPR1 and MAPK pathway-related genes were determined by RT-qPCR and western blot analysis. MTT assay was performed to evaluate cell proliferation and flow cytometry to evaluate cell cycle progression and apoptosis. GSE19804 and GSE27262 were screened from Gene Expression Omnibus database. FPR1 was higher in patients with I/R injury and activate the MAPK signaling pathway. FRP1 gene silencing decreased CVF value, infarct area, apoptotic index, positive expression rates of FPR1 and MAPK, decreased FPR1, p38, ERK, JNK, MMP-2, TIMP-2, NF-kB, Bax, p-p38, p-ERK, and p-JNK levels, increased Bcl-2 level, promoted cell proliferation and cell cycle progression, and inhibited cell apoptosis rate. Overall, our study demonstrates that the silencing of FPR1 gene depresses inflammation, cardiomyocyte apoptosis and ventricular remodeling in rats with I/R injury through the suppressing the activation of the MAPK signaling pathway.

journal_name

Exp Cell Res

journal_title

Experimental cell research

authors

Zhou QL,Teng F,Zhang YS,Sun Q,Cao YX,Meng GW

doi

10.1016/j.yexcr.2018.07.016

subject

Has Abstract

pub_date

2018-09-15 00:00:00

pages

506-518

issue

eissn

0014-4827

issn

1090-2422

pii

S0014-4827(18)30442-7

journal_volume

370

pub_type

杂志文章

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FPR1 gene silencing suppresses cardiomyocyte apoptosis and ventricular remodeling in rats with ischemia/reperfusion injury through the inhibition of MAPK signaling pathway.