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Deprecated: Implicit conversion from float 278.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Gut+Liver 2018 ; 12 (4): 449-56 Nephropedia Template TP
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Expression of Fibroblast Growth Factor 21 and ?-Klotho Regulates Hepatic Fibrosis through the Nuclear Factor-?B and c-Jun N-Terminal Kinase Pathways #MMPMID29699061
Lee KJ; Jang YO; Cha SK; Kim MY; Park KS; Eom YW; Baik SK
Gut Liver 2018[Jul]; 12 (4): 449-56 PMID29699061show ga
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 ?-Klotho and FGF21 pathway in the liver. Methods: Enrolled patients had biopsy-confirmed viral or alcoholic hepatitis. FGF19, FGF21 and ?-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-?B (NF-?B) 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 1? [IL-1?], IL-6, and tumor necrosis factor-?) were positively correlated, while ?-Klotho expression was negatively correlated with the degree of fibrosis. In Huh-7 cells, IL-1? increased FGF21 levels and decreased ?-Klotho levels. NF-?B and JNK inhibitors abolished the effect of IL-1? on both FGF21 and ?-Klotho expression. FGF21 protected IL-1?-induced growth retardation in Huh-7 cells. Conclusions: These results indicate that the inflammatory response during fibrogenesis increases FGF21 levels and suppresses ?-Klotho via the NF-?B and JNK pathway. In addition, FGF21 likely protects hepatocytes from hepatic inflammation and fibrosis.