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.
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 murinehepatic 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.
Authors: Rebecca T Marquez; Sarmistha Bandyopadhyay; Erik B Wendlandt; Kathy Keck; Brandon A Hoffer; Michael S Icardi; Randolph N Christensen; Warren N Schmidt; Anton P McCaffrey Journal: Lab Invest Date: 2010-07-12 Impact factor: 5.662
Authors: K Ishak; A Baptista; L Bianchi; F Callea; J De Groote; F Gudat; H Denk; V Desmet; G Korb; R N MacSween Journal: J Hepatol Date: 1995-06 Impact factor: 25.083
Authors: Katey J Rayner; Yajaira Suárez; Alberto Dávalos; Saj Parathath; Michael L Fitzgerald; Norimasa Tamehiro; Edward A Fisher; Kathryn J Moore; Carlos Fernández-Hernando Journal: Science Date: 2010-05-13 Impact factor: 47.728