MicroRNA-377 Mediates Cardiomyocyte Apoptosis Induced by Cyclosporin A
| Autor: | Jin-Yu Chi, Hui Zou, Xin-Hua Yin, Hai-Hai Liang, Zi-Dan Guo, Long-Tao Huangfu, Xiao-Duo Zhu |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Apoptosis X-Linked Inhibitor of Apoptosis Protein 03 medical and health sciences 0302 clinical medicine Cyclosporin a microRNA Medicine Myocyte Animals Myocytes Cardiac Rats Wistar Cells Cultured Kidney business.industry Microarray analysis techniques XIAP Neuropilin-2 MicroRNAs 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Immunology Toxicity Cancer research Cyclosporine Cardiology and Cardiovascular Medicine business Immunosuppressive Agents |
| Zdroj: | The Canadian journal of cardiology. 32(10) |
| ISSN: | 1916-7075 |
| Popis: | Cyclosporin A (CsA) is a potent immunosuppressant that has wide clinical applications for autoimmune disorders and prevention of rejection in organ transplantation. However, its liver, kidney, and heart toxicity has limited its use. In this study, we investigated the mechanism by which CsA induced cardiomyocyte apoptosis. Through microarray analysis, we found that the expression of microRNA (miR)-377 was regulated by CsA. Ectopic overexpression of miR-377 led to increased apoptosis in cardiomyocytes, as evidenced by an increased number of apoptotic cells, increased levels of proapoptotic proteins, decreased levels of antiapoptotic proteins, and elevated caspase pathway activity. We also found that miR-377 was required for CsA-induced apoptosis, because inhibition of miR-377 expression markedly reduced the ability of CsA to induce cardiomyocyte apoptosis. In addition, we identified XIAP and NRP2 as direct targets for miR-377. The expression levels of these 2 antiapoptotic proteins were negatively regulated by miR-377, as well as by CsA both in vitro and in vivo . Our data suggested that CsA induced cardiomyocyte apoptosis through the miR-377–XIAP / NRP2 axis. |
| Databáze: | OpenAIRE |
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