Fibroblast Growth Factor–21 ameliorates hepatic encephalopathy by activating the STAT3-SOCS3 pathway to inhibit activated hepatic stellate cells

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Yeboah Kwaku Opoku
Zhihang Liu
Justice Afrifa
Asare Kwame Kumi
Han Liu
George Ghartey-Kwansah
Harriet Koranteng
Xinghao Jiang
Guiping Ren
Deshan Li

Abstract

Neurological dysfunction, one of the consequences of acute liver failure (ALF), and also referred to as hepatic encephalopathy (HE), contributes to mortality posing challenges for clinical management. FGF21 has been implicated in the inhibition of cognitive decline and fibrogenesis. However, the effects of FGF21 on the clinical and molecular presentations of HE has not been elucidated. HE was induced by fulminant hepatic failure using thioacetamide (TAA) in male C57BL/6J mice while controls were injected with saline. For two consecutive weeks, mice were treated intraperitoneally with FGF21 (3 mg/kg) while controls were treated with saline. Cognitive, neurological, and activity function scores were recorded. Serum, liver, and brain samples were taken for analysis of CCL5 and GABA by ELISA, and RT qPCR was used to measure the expressions of fibrotic and pro-inflammatory markers. We report significant improvement in both cognitive and neurological scores by FGF21 treatment after impairment by TAA. GABA and CCL5, key factors in the progression of HE were also significantly reduced in the treatment group. Furthermore, the expression of fibrotic markers such as TGFβ and Col1 were also significantly downregulated after FGF21 treatment. TNFα and IL-6 were significantly reduced in the liver while in the brain, TNFα and IL-1 were downregulated. However, both in the liver and the brain, IL-10 was significantly upregulated. FGF21 inhibits CXCR4/CCL5 activation and upregulates the production of IL-10 in the damaged liver stimulating the production pro-inflammatory cytokines and apoptosis of hepatic stellate cells through the STAT3-SOCS3 pathway terminating the underlying fibrosis in HE.

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How to Cite
Opoku, Y., Liu, Z., Afrifa, J., Kumi, A., Liu, H., Ghartey-Kwansah, G., Koranteng, H., Jiang, X., Ren, G., & Li, D. (2020). Fibroblast Growth Factor–21 ameliorates hepatic encephalopathy by activating the STAT3-SOCS3 pathway to inhibit activated hepatic stellate cells. EXCLI Journal, 19, 567-581. https://doi.org/10.17179/excli2020-1287
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