The protective effects of fibroblast growth factor 10 against hepatic ischemia-reperfusion injury in mice.
The protective effects of fibroblast growth factor 10 against hepatic ischemia-reperfusion injury in mice.
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成纤维细胞生长因子10对小鼠肝脏缺血再灌注损伤的保护作用
DOI：
10.1016/j.redox.2021.101859
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发表时间：
2021-04
期刊：
影响因子：
11.4
通讯作者：
Cong W
中科院分区：
文献类型：
--
作者：
Li S;Zhu Z;Xue M;Pan X;Tong G;Yi X;Fan J;Li Y;Li W;Dong Y;Shen E;Gong W;Wang X;Yu Y;Maeng YJ;Li X;Lee KY;Jin L;Cong W
Hepatic ischemia-reperfusion injury (IRI) is a major complication of liver surgery and transplantation. IRI leads to hepatic parenchymal cell death, resulting in liver failure, and lacks effective therapeutic approaches. Fibroblast growth factor 10 (FGF10) is a paracrine factor which is well-characterized with respect to its pro-proliferative effects during embryonic liver development and liver regeneration, but its role in hepatic IRI remains unknown. In this study, we investigated the role of FGF10 in liver IRI and identified signaling pathways regulated by FGF10. In a mouse model of warm liver IRI, FGF10 was highly expressed during the reperfusion phase. In vitro experiments demonstrated that FGF10 was primarily secreted by hepatic stellate cells and acted on hepatocytes. The role of FGF10 in liver IRI was further examined using adeno-associated virus-mediated gene silencing and overexpression. Overexpression of FGF10 alleviated liver dysfunction, reduced necrosis and inflammation, and protected hepatocytes from apoptosis in the early acute injury phase of IRI. Furthermore, in the late phase of IRI, FGF10 overexpression also promoted hepatocyte proliferation. Meanwhile, gene silencing of FGF10 had the opposite effect. Further studies revealed that overexpression of FGF10 activated nuclear factor-erythroid 2-related factor 2 (NRF2) and decreased oxidative stress, mainly through activation of the phosphatidylinositol-3-kinase/AKT pathway, and the protective effects of FGF10 overexpression were largely abrogated in NRF2 knockout mice. These results demonstrate the protective effects of FGF10 in liver IRI, and reveal the important role of NRF2 in FGF10-mediated hepatic protection during IRI. FGF10 is markedly upregulated in the early phase of liver IRI. FGF10 overexpression exerts great potential in ameliorating hepatic IRI. FGF10 knockdown significantly aggravates hepatic IRI. FGF10 overexpression activates PI3K/AKT-NRF2 signaling and thus ameliorates hepatic IRI. NRF2 knockout abrogates the protective effects of FGF10 overexpression during liver IRI.
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神经元源性 FGF10 通过抑制 NF-κ B 依赖性神经炎症和激活 PI3K/Akt 存活信号通路改善小鼠脑缺血损伤
影响因子：
4.6
作者：
Li YH;Fu HL;Tian ML;Wang YQ;Chen W;Cai LL;Zhou XH;Yuan HB
通讯作者：
Yuan HB
影响因子：
25.7
作者：
Gandhi CR
通讯作者：
Gandhi CR
影响因子：
64.5
作者：
Manning BD;Toker A
通讯作者：
Toker A
KGFR-Akt-mTOR-Nrf2 信号传导的激活可保护人视网膜色素上皮细胞免受紫外线侵害
DOI：
10.1016/j.bbrc.2017.12.078
发表时间：
2018-01-15
影响因子：
3.1
作者：
Hu, Haitao;Hao, Lanxiang;Yao, Jin
通讯作者：
Yao, Jin
影响因子：
13.5
作者：
Kuboki, Satoshi;Shin, Thomas;Lentsch, Alex B.
通讯作者：
Lentsch, Alex B.