Expression of Fibroblast Growth Factor 21 and β-Klotho Regulates Hepatic Fibrosis through the Nuclear Factor-κB and c-Jun N-Terminal Kinase Pathways
Gut and Liver
;
: 449-456, 2018.
Article
in English
| WPRIM
| ID: wpr-715587
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Fibrosis
/
RNA, Messenger
/
Enzyme-Linked Immunosorbent Assay
/
Blotting, Western
/
NF-kappa B
/
Interleukin-6
/
MAP Kinase Signaling System
/
Hepatocytes
/
JNK Mitogen-Activated Protein Kinases
/
Interleukin-1beta
Limits:
Humans
Language:
English
Journal:
Gut and Liver
Year:
2018
Type:
Article
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