Abstract
Background
Chronic hepatitis B virus (HBV) infection, which can lead to hepatic disease, has become a critical national healthcare problem, and many people die each year as a result of HBV infection and its complications. Although microRNA-33a (miR-33a) is a novel modulator of lipid and cholesterol metabolism, the role of miR-33a in the hepatic fibrogenesis is still unknown. Here, we aimed to explore the roles and mechanisms of miR-33a in liver fibrosis.
Methods
miR-33a expression in whole liver and serum samples was measured from chronic hepatitis B (CHB) patients by quantitative real-time PCR (qRT-PCR). In addition, different murine hepatic fibrosis models were produced to consolidate the results in human tissue. Human and murine primary liver fibrosis-associated cells were isolated and treated with transforming growth factor-β1 (TGF-β1).
Results
miR-33a expression levels in liver tissue significantly increased with a fibrosis progression manner in the human liver. Furthermore, serum miR-33a levels associated positively with progressing process of hepatic fibrosis. miR-33a was in particular increased in hepatic stellate cells (HSC) than other liver fibrosis-associated cells. Stimulation of HSCs with TGF-β1 leads to a critical increase of miR-33a. Increasing miR-33a levels increased (whereas inhibiting miR-33a weakened) the activation role of TGF-β1 in LX-2 cells, which might be a potential mechanism through moderating Smad7 expression.
Conclusions
miR-33a may be a novel marker for HSC activation and hepatic fibrosis progress, suggesting a new therapeutic target in liver fibrosis.
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Huang, CF., Sun, CC., Zhao, F. et al. miR-33a levels in hepatic and serum after chronic HBV-induced fibrosis. J Gastroenterol 50, 480–490 (2015). https://doi.org/10.1007/s00535-014-0986-3
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DOI: https://doi.org/10.1007/s00535-014-0986-3