MiR-21 suppression prevents cardiac alterations induced by d-galactose and doxorubicin. (February 2018)

• Record Type: Journal Article
• Authors: Bei, Yihua; Wu, Xiaoting; Cretoiu, Dragos; Shi, Jing; Zhou, Qiulian; Lin, Shenghui; Wang, Hui; Cheng, Yan; Zhang, Haifeng; Xiao, Junjie; Li, Xinli
• Is Part Of: Journal of molecular and cellular cardiology. Volume 115(2018)
• Page Start: 130
• Page End: 141
• Publication Date: 2018-02
• Subjects: d-galactose-induced aging -- Doxorubicin -- miR-21 -- Phosphatase and tensin homolog; Cardiology -- Periodicals; Heart Diseases -- Periodicals; Molecular Biology -- Periodicals; Cardiologie -- Périodiques; Cardiology; Electronic journals; Periodicals; 616.12
• DOI: 10.1016/j.yjmcc.2018.01.007
• Languages: English
• ISSNs: 0022-2828

Abstract

Abstract: d -galactose (d -gal)-induced cardiac alterations and Doxorubicin (Dox)-induced cardiomyocyte senescence are commonly used models to study cardiac aging. Accumulating evidence has suggested that microRNAs (miRNAs, miRs) are critically involved in the regulation of cellular and organismal aging and age-related diseases. However, little has been revealed about the roles of miRNAs in cardiac alterations induced byd -gal and Dox. In this study, we used miRNA arrays to investigate the dysregulated miRNAs in heart samples from 15 month-old versus 2 month-old male C57BL/6 mice and further validated them ind -gal-induced pseudo-aging mouse model and Dox-induced cardiomyocyte senescence in vitro model. We confirmed a significant increase of miR-21 in all these models by quantitative reverse transcription polymerase chain reactions. We further demonstrated that miR-21 was able to promote Dox-induced cardiomyocyte senescence whereas suppression of miR-21 could prevent that, as determined by percentage of β-gal-positive cells and gene markers of aging. Phosphatase and tensin homolog (PTEN) was identified as a target gene of miR-21, mediating its effect in increasing cardiomyocyte senescence. Finally, we found that miR-21 knockout mice were resistant tod -gal-induced alterations in aging-markers and cardiac function. Collectively, this study provides direct evidence that inhibition of miR-21 is protective againstd -gal-induced cardiac alterations and Dox-induced cardiomyocyte senescence via targeting PTEN. Inhibition of miR-21 might be a novel strategy to combat cardiac aging. Highlights: miR-21 suppression protects against Doxorubicin-induced cardiomyocyte senescence. miR-21 knockout mice are resistant to D-galactose-induced cardiac pseudo-aging. PTEN is a target gene of miR-21 in the regulation of cardiomyocyte senescence. Inhibition of miR-21 might be a novel strategy to combat cardiac aging.