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  • Title: Basic fibroblast growth factor protects against liver ischemia-reperfusion injury via the Nrf2/Hippo signaling pathway.
    Author: Chen X, Tong G, Chen S.
    Journal: Tissue Cell; 2022 Dec; 79():101921. PubMed ID: 36150335.
    Abstract:
    Liver ischemia-reperfusion injury (IRI) continues to play a major role in liver dysfunction and failure, which is involved in the process of liver transplantation, partial hepatectomy, and hemorrhagic shock. Basic fibroblast growth factor (bFGF) is involved in a variety of biological processes. However, bFGF's role in hepatic IRI remains unclear. In our study, we constructed hepatic I/R surgery in WT and nuclear factor-erythroid 2-related factor 2 (Nrf2) KO mice and hypoxia-reoxygenation (H/R) model in AML12 cells to research bFGF's possible role. We found that the expression level of bFGF was highly upregulated in livers after hepatic IRI. In vivo, bFGF treatment led to a significant reduction in the necrotic area, accompanied by alleviation of oxidative stress, cell apoptosis, and inflammation in WT mice. bFGF-induced Nrf2 nuclear translocation and its downstream anti-oxidative proteins production in AML12 cells provide a mechanistic explanation for this phenomenon. In addition, bFGF-induced Nrf2 activation via the protein kinase B (AKT)/glycogen synthase kinase-3β (GSK-3β) pathway. bFGF activated Nrf2 to restrain the phosphorylation of promote Yes-associated protein (YAP) and YAP stabilization, thus reducing cell apoptosis and inflammation in ROS-dependent manner, revealed that Hippo signaling was the downstream of Nrf2 mediating protective effects of bFGF during hepatic IRI. In conclusion, our findings suggest that bFGF could reduce hepatic IRI and hepatocyte injury via the Nrf2/Hippo signaling pathway.
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