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- Title
Expression of Fibroblast Growth Factor 21 and β-Klotho Regulates Hepatic Fibrosis through the Nuclear Factor-κB and c-Jun N-Terminal Kinase Pathways.
- Authors
Kyong Joo Lee; Yoon Ok Jang; Seung-Kuy Cha; Moon Young Kim; Kyu-Sang Park; Young Woo Eom; Soon Koo Baik
- 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, realtime 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 Nterminal 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.
- Subjects
HEPATIC fibrosis; FIBROBLAST growth factors; NF-kappa B; C-Jun N-terminal kinases; ENZYME-linked immunosorbent assay; DIAGNOSIS
- Publication
Gut & Liver, 2018, Vol 12, Issue 4, p449
- ISSN
1976-2283
- Publication type
Article
- DOI
10.5009/gnl17443