Expression of Fibroblast Growth Factor 21 and β-Klotho Regulates Hepatic Fibrosis through the Nuclear Factor-κB and c-Jun N-Terminal Kinase Pathways.
- Author:
Kyong Joo LEE
1
;
Yoon Ok JANG
;
Seung Kuy CHA
;
Moon Young KIM
;
Kyu Sang PARK
;
Young Woo EOM
;
Soon Koo BAIK
Author Information
- Publication Type:Original Article
- Keywords: Fibroblast growth factor 21; β-Klotho; Interleukin-1beta; NF-kappa B; JNK
- MeSH: Blotting, Western; Enzyme-Linked Immunosorbent Assay; Fibroblast Growth Factors*; Fibroblasts*; Fibrosis*; Hepatitis, Alcoholic; Hepatocytes; Humans; Inflammation; Interleukin-1beta; Interleukin-6; JNK Mitogen-Activated Protein Kinases*; Liver; MAP Kinase Signaling System; Necrosis; NF-kappa B; Real-Time Polymerase Chain Reaction; RNA, Messenger
- From:Gut and Liver 2018;12(4):449-456
- CountryRepublic of Korea
- Language:English
- Abstract: 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.
