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Caffeine attenuates liver fibrosis via defective adhesion of hepatic stellate cells in cirrhotic model

Authors


Abstract

Background and Aim

Several epidemiological studies have shown that coffee intake attenuates the progression of liver fibrosis; however, the mechanism is unclear.

Aims

We investigated the direct effects of caffeine on hepatic stellate cells (HSCs) and assessed whether caffeine attenuated intrahepatic fibrosis in rat model of liver cirrhosis.

Methods

Human hepatic stellate cell line, an immortalized human HSCs line, was used in in vitro assay system. Cell migration and proliferation were assessed in presence of various caffeine concentrations (0, 1, 5, and 10 mmol), and levels of procollagen type Ic and α-smooth muscle actin (α-SMA) were measured by Western blot. Severity of liver inflammation and fibrosis were compared between thioacetamide-treated rats with and without caffeine supplementation.

Results

Caffeine increased HSCs apoptosis and intracellular F-actin and cyclic adenosine monophosphate expression. Caffeine also inhibited procollagen type Ic and α-SMA expression in a dose- and time-dependent manner. In rat model, caffeine decreased periportal inflammation, levels of inflammatory cells (1.4 ± 0.52 vs 2.6 ± 0.46, P < 0.05), and fibrosis (2.1 ± 0.35 vs 2.9 ± 0.84, P < 0.05). Transforming growth factor-β and α-SMA expressions were also reduced by caffeine.

Conclusion

Caffeine attenuates the progression of liver fibrosis by inhibiting HSCs adhesion and activation.

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