| Autor: |
Ji Xiao, Qian Yang, Ye’an Zhang, Haoran Xu, Yang Ye, Linchao Li, Yi Yang, Shengwei Jin |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
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| Zdroj: |
Cell & Bioscience, Vol 11, Iss 1, Pp 1-14 (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2045-3701 |
| DOI: |
10.1186/s13578-021-00734-x |
| Popis: |
Abstract Background Ferroptosis is unique among different types of regulated cell death and closely related to organ injury. Whether ferroptosis occurs in sepsis-associated acute kidney injury (SA-AKI) is not clear. Nuclear factor-erythroid-2-related factor 2 (Nrf2) is crucial to the regulation of ferroptosis. We and others have shown that Maresin conjugates in tissue regeneration 1 (MCTR1) or other members of specialized pro-resolving mediators (SPMs) can actively regulate inflammation resolution and protect organs against injury in inflammatory diseases by activating the Nrf2 signaling. The aim of this study was to determine whether ferroptosis occurs in SA-AKI. Furthermore, we investigated the potential role and mechanism of MCTR1 in the regulation of ferroptosis in SA-AKI, which mainly focus on the Nrf2 signaling. Results We demonstrated for the first time that ferroptosis is present in SA-AKI. Moreover, MCTR1 effectively suppressed ferroptosis in SA-AKI. Meanwhile, MCTR1 upregulated the expression of Nrf2 in the kidney of septic mice. Nrf2 inhibitor ML-385 reversed MCTR1-regulated ferroptosis and AKI, implying that Nrf2 is involved in the inhibitory effects of MCTR1 on ferroptosis in SA-AKI. Further, MCTR1 inhibited ferroptosis and elevated the expression of Nrf2 in LPS-induced HK-2 cells. However, Nrf2 siRNA offset the effect of MCTR1 on ferroptosis. Finally, we observed that MCTR1 ameliorates multi-organ injury and improves survival in animal models of sepsis. Conclusions These data demonstrate that MCTR1 suppresses ferroptosis in SA-AKI through the Nrf2 signaling. Our study enriches the pathophysiological mechanism of SA-AKI and provides new therapeutic ideas and potential intervention targets for SA-AKI. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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