| Autor: |
Runze Wang, Yuerong Xu, Xiaolin Niu, Yexian Fang, Dong Guo, Jiangwei Chen, Hanzhao Zhu, Jiaying Dong, Ran Zhao, Ying Wang, Bingchao Qi, Gaotong Ren, Xue Li, Li Liu, Mingming Zhang |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
Frontiers in Physiology, Vol 12 (2021) |
| Druh dokumentu: |
article |
| ISSN: |
1664-042X |
| DOI: |
10.3389/fphys.2021.646903 |
| Popis: |
Doxorubicin (DOX) cardiotoxicity is a life-threatening side effect that leads to a poor prognosis in patients receiving chemotherapy. We investigated the role of miR-22 in doxorubicin-induced cardiomyopathy and the underlying mechanism in vivo and in vitro. Specifically, we designed loss-of-function and gain-of-function experiments to identify the role of miR-22 in doxorubicin-induced cardiomyopathy. Our data suggested that inhibiting miR-22 alleviated cardiac fibrosis and cardiac dysfunction induced by doxorubicin. In addition, inhibiting miR-22 mitigated mitochondrial dysfunction through the sirt1/PGC-1α pathway. Knocking out miR-22 enhanced mitochondrial biogenesis, as evidenced by increased PGC-1α, TFAM, and NRF-1 expression in vivo. Furthermore, knocking out miR-22 rescued mitophagy, which was confirmed by increased expression of PINK1 and parkin and by the colocalization of LC3 and mitochondria. These protective effects were abolished by overexpressing miR-22. In conclusion, miR-22 may represent a new target to alleviate cardiac dysfunction in doxorubicin-induced cardiomyopathy and improve prognosis in patients receiving chemotherapy. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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