| First Author | Xiao M | Year | 2022 |
| Journal | Redox Biol | Volume | 49 |
| Pages | 102219 | PubMed ID | 34990928 |
| Mgi Jnum | J:322599 | Mgi Id | MGI:6853989 |
| Doi | 10.1016/j.redox.2021.102219 | Citation | Xiao M, et al. (2022) A new FGF1 variant protects against adriamycin-induced cardiotoxicity via modulating p53 activity. Redox Biol 49:102219 |
| abstractText | A cumulative and progressively developing cardiomyopathy induced by adriamycin (ADR)-based chemotherapy is a major obstacle for its clinical application. However, there is a lack of safe and effective method to protect against ADR-induced cardiotoxicity. Here, we found that mRNA and protein levels of FGF1 were decreased in ADR-treated mice, primary cardiomyocytes and H9c2 cells, suggesting the potential effect of FGF1 to protect against ADR-induced cardiotoxicity. Then, we showed that treatment with a FGF1 variant (FGF1(DeltaHBS)) with reduced proliferative potency significantly prevented ADR-induced cardiac dysfunction as well as ADR-associated cardiac inflammation, fibrosis, and hypertrophy. The mechanistic study revealed that apoptosis and oxidative stress, the two vital pathological factors in ADR-induced cardiotoxicity, were largely alleviated by FGF1(DeltaHBS) treatment. Furthermore, the inhibitory effects of FGF1(DeltaHBS) on ADR-induced apoptosis and oxidative stress were regulated by decreasing p53 activity through upregulation of Sirt1-mediated p53 deacetylation and enhancement of murine double minute 2 (MDM2)-mediated p53 ubiquitination. Upregulation of p53 expression or cardiac specific-Sirt1 knockout (Sirt1-CKO) almost completely abolished FGF1(DeltaHBS)-induced protective effects in cardiomyocytes. Based on these findings, we suggest that FGF1(DeltaHBS) may be a potential therapeutic agent against ADR-induced cardiotoxicity. |
