Luteolin-Mediated Inhibition of Hepatic Stellate Cell Activation via Suppression of the STAT3 Pathway

Hepatic stellate cell (HSC) activation is responsible for hepatic fibrogenesis and is associated with an overexpression of transcription 3 (STAT3). Luteolin, a common dietary flavonoid with potent anti-inflammatory properties, has previously demonstrated antifibrogenic properties in HSCs but the mec...

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Published in:International journal of molecular sciences 2018-05, Vol.19 (6), p.1567
Main Authors: Cummins, Claire B, Wang, Xiaofu, Nunez Lopez, Omar, Graham, Gabriel, Tie, Hong-Yan, Zhou, Jia, Radhakrishnan, Ravi S
Format: Article
Language:English
Subjects:
Actin
Anti-inflammatory agents
c-Myc protein
Cell activation
Cell lines
Cell proliferation
Collagen (type I)
Cyclin D1
Fibronectin
hepatic fibrosis
hepatic stellate cells
Immunofluorescence
Inflammation
Liver
luteolin
Muscles
Myc protein
Nuclear transport
Proteins
Rodents
Smooth muscle
STAT3
Stat3 protein
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Summary:Hepatic stellate cell (HSC) activation is responsible for hepatic fibrogenesis and is associated with an overexpression of transcription 3 (STAT3). Luteolin, a common dietary flavonoid with potent anti-inflammatory properties, has previously demonstrated antifibrogenic properties in HSCs but the mechanism has not been fully elucidated. Activated human and rat hepatic stellate cell lines LX-2 and HSC-T6 were used to study the effects of luteolin on HSCs. Cellular proteins were determined by western blot and immunofluorescence. Cell proliferation was assessed with Alamar Blue assay. Luteolin significantly decreased LX-2 and HSC-T6 cell viability in a time-and-dose-dependent manner, as well as decreased HSC end-products α-smooth muscle actin (α-SMA), collagen I, and fibronectin. Luteolin decreased levels of total and phosphorylated STAT3, suppressed STAT3 nuclear translocation and transcriptional activity, and attenuated expression of STAT3-regulated proteins c-myc and cyclin D1. STAT3 specific inhibitors stattic and SH-4-54 demonstrated similar effects on HSC viability and α-SMA production. In LX-2 and HSC-T6 cells, luteolin demonstrates a potent ability to inhibit hepatic fibrogenesis via suppression of the STAT3 pathway. These results further elucidate the mechanism of luteolin as well as the effect of the STAT3 pathway on HSC activation.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms19061567