Abstract
Heart failure (HF) is a rising epidemic and public health burden in modern society. It is of great need to find new biomarkers to ensure a timely diagnosis and to improve treatment and prognosis of the disease. The mouse model of HF was established by thoracic aortic constriction. Color Doppler ultrasound was performed to detect left ventricular end-diastolic diameter. Hematoxylin and eosin staining was conducted to observe the pathological changes of mouse myocardium. The RT-qPCR analysis was performed to detect miR-590-5p and RTN4 expression levels. Western blot was conducted to detect protein levels of the indicated genes. We found that the expression of miR-590-5p was downregulated in cardiac tissues of HF mice. Injection of AAV-miR-590-5p attenuated myocardium hypertrophy and myocyte apoptosis. Additionally, miR-590-5p overexpression promoted viability, inhibited apoptosis, and decreased ANF, BNP and beta-MHC protein levels in H9c2 cell. Mechanistically, miR-590-5p binds to RTN4 3′‐untranslated region, as predicted by starBase online database and evidenced by luciferase reporter assay. Furthermore, miR-590-5p negatively regulates RTN4 mRNA expression and suppresses its translation. The final rescue experiments revealed that miR-590-5p modulated cardiomyocyte phenotypes by binding to RTN4. In conclusion, miR-590-5p modulates myocardium hypertrophy and myocyte apoptosis in HF by downregulating RTN4.
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10735_2021_10009_MOESM1_ESM.tif
Supplementary file1 Expression of miR-590-5p and RTN4 in adrenal, brain, fat, kidney, andsmall intestine tissues. A. Based on “HPA RNA-seq normal tissues” project (RNA-seq was performedof tissue samples from 95 human individuals representing 27 different tissues to determine tissuespecificityof all protein-coding genes), expression of RTN4 in 27 different tissues was identified (datawas obtained from NCBI). B-C. Expression of RTN4 and miR-590-5p in adrenal, brain, fat, kidney, andsmall intestine tissues isolated from sham mice and HF mice (TIF 596 kb)
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Fan, P., Zhang, L., Cheng, T. et al. MiR-590-5p inhibits pathological hypertrophy mediated heart failure by targeting RTN4. J Mol Histol 52, 955–964 (2021). https://doi.org/10.1007/s10735-021-10009-x
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DOI: https://doi.org/10.1007/s10735-021-10009-x