MiR-150-5p retards the progression of myocardial fibrosis by targeting EGR1

Abstract

To investigate the differential expression of microRNA-150-5p (miR-150-5p) and early growth response 1 (EGR1) in myocardial fibrosis (MF) cells, and determine the effect between miR-150-5p and EGR1 on MF. Human MF cells were generated via Trypanosoma cruzi (T. cruzi) infection, a mouse model of MF was generated via angiotensin II. The expression levels of miR-150-5p and EGR1 were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot assay. The correlation between miR-150-5p and EGR1 was confirmed by a luciferase reporter assay. The viability, proliferation, and apoptotic rate were detected by cell counting kit-8 (CCK-8), colony-formation and flow cytometry assays. Hematoxylin-eosin (HE) staining and Masson staining visualized the degree of MF. Echocardiography was performed to obtain the levels of left ventricle fractional shortening (LVFS) and left ventricle ejection fraction (LVEF), computer algorithms and a videographics program were used to obtain the levels of left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP) and ±left ventricular dp/dt maximum (LV dp/dtmax). We found that the expression of miR-150-5p in MF cells was lower than normal cardiomyocytes, while the expression level of EGR1 in MF cells were higher than normal cardiomyocytes. Cell experiments demonstrated that EGR1 and miR-150-5p could influence the development of MF, and the expression of EGR1 in cardiomyocytes was regulated by miR-150-5p directly. Lastly, we confirmed that sh-Egr1 would decrease the severity of MF, while miR-150-5p antagomir could aggravate MF. Our results illustrate the mechanism of MF development, and provide a potential target for MF treatment.

EGR1 Transcription Factor is a Multifaceted Regulator of Matrix Production in Tendons and Other Connective Tissues

“…Notably, Egr1 transcription is activated in hypoxic and ischemic conditions in heart and in calcified heart valves [151,152]. The miR-150-5p retards the progression of myocardial fibrosis by targeting EGR1 [153].…”

Correlations of circulating miR-26b level with left ventricular hypertrophy and cardiac function in elderly patients with hypertension

“… 11 The roles of miRNAs in diseases such as viral diseases, digestive system, nervous system and reproductive system are well-documented. 12 They have been involved in cardiac development and remodeling, and are closely related to various cardiovascular diseases such as myocardial fibrosis, myocardial hypertrophy and heart failure. 13 The expression level of miR-26b in patients with coronary heart disease is significantly lower than that in healthy people, and miR-26b is expected to become a marker for the diagnosis of coronary heart disease.…”

Circulating MicroRNAs: Biogenesis and Clinical Significance in Acute Myocardial Infarction

“…Many studies on the diagnostic role of circulating miRNAs in AMI were initially based on big data analysis, but follow-up studies have also confirmed their relationship with cardiovascular disease which we will not discuss it here ( Liu W. L. et al, 2015 ; Wei L. X. et al, 2015 ; Xue et al, 2015 ; He and Huang, 2017 ; Besnier et al, 2019 ; Che et al, 2019 ; Li X. D. et al, 2019 ; Shen et al, 2019 ; Zhang et al, 2019 ). Meder et al (2011) identified two downregulated miRNAs, miR-1291 and miR-663b, among 121 miRNAs related to AMI through whole genome miRNA expression profiling.…”