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KMID : 1188320180120040449
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Gut and Liver
2018 Volume.12 No. 4 p.449 ~ p.456
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Expression of Fibroblast Growth Factor 21 and β-Klotho Regulates Hepatic Fibrosis through the Nuclear Factor-κB and c-Jun N-Terminal Kinase Pathways
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Lee Kyong-Joo
Jang Yoon-Ok
Cha Seung-Kuy
Kim Moon-Young
Park Kyu-Sang
Eom Young-Woo
Baik Soon-Koo
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Abstract
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Background/Aims: Fibroblast growth factor (FGF) 21 is associated with hepatic inflammation and fibrosis. However, little is known regarding the effects of inflammation and fibrosis on the β-Klotho and FGF21 pathway in the liver.
Methods: Enrolled patients had biopsy-confirmed viral or alcoholic hepatitis. FGF19, FGF21 and β-Klotho levels were evaluated using enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and Western blotting. Furthermore, we explored the underlying mechanisms for this process by evaluating nuclear factor-κB (NF-κB) and c-Jun N-terminal kinase (JNK) pathway involvement in Huh-7 cells.
Results: We observed that the FGF19 and FGF21 serum and mRNA levels in the biopsied liver tissue gradually increased and were correlated with fibrosis stage. Inflammatory markers (interleukin 1β [IL-1β], IL-6, and tumor necrosis factor-α) were positively correlated, while β-Klotho expression was negatively correlated with the degree of fibrosis. In Huh-7 cells, IL-1β increased FGF21 levels and decreased β-Klotho levels. NF-κB and JNK inhibitors abolished the effect of IL-1β on both FGF21 and β-Klotho expression. FGF21 protected IL-1β-induced growth retardation in Huh-7 cells.
Conclusions: These results indicate that the inflammatory response during fibrogenesis increases FGF21 levels and suppresses β-Klotho via the NF-κB and JNK pathway. In addition, FGF21 likely protects hepatocytes from hepatic inflammation and fibrosis.
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KEYWORD
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Fibroblast growth factor 21, β-Klotho, Interleukin-1beta, NF-kappa B, JNK
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