Abstract
To investigate the roles and mechanisms of miR-33a in liver fibrosis, 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, Human and murine primary liver fibrosis-associated cells were isolated and treated with transforming growth factor-β1 (TGF-β1). We found that 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. Altogether, data suggest that miR-33a may be a novel marker for HSC activation and hepatic fibrosis progress, suggesting a new therapeutic target in liver fibrosis.
Highlights
A microRNA is a small newly discovered endogenous non-coding RNA molecule that contains 18–25 nucleotides and perform as post-transcriptional regulators of target genes by binding to the 3’untranslated region (3’UTR) mRNA [5,6,7]. microRNA-33a recently has become a hot research small miRNA and it has been demonstrated that it regulates lipid homeostasis [8,9,10,11], and may be exerting as a potent tumor suppressor [12], cell proliferation and cycling [13]
Li et al [14] recently demonstrated that miR-33a-associated hepatic stellate cells (HSC) activation and extracellular matrix production was, at least in part, modulated by the activation of the PI3K/Akt pathway and PPAR-α in vitro, and they found that the expression of miR-33a was associated with the progression of liver fibrosis
Our results showed that serum and hepatic miR-33a levels increased with the progression of liver fibrosis in chronic hepatitis B (CHB) patients and expression of miR-33a was significantly upregulated in primary hepatocytes and hepatic stellate cells from C57BL/6 murine hepatic fibrosis models as previously described [15,16,17]
Summary
A microRNA (miRNA) is a small newly discovered endogenous non-coding RNA molecule that contains 18–25 nucleotides and perform as post-transcriptional regulators of target genes by binding to the 3’untranslated region (3’UTR) mRNA [5,6,7]. microRNA-33a (miR-33a) recently has become a hot research small miRNA and it has been demonstrated that it regulates lipid homeostasis [8,9,10,11], and may be exerting as a potent tumor suppressor [12], cell proliferation and cycling [13]. To investigate the roles and mechanisms of miR-33a in liver fibrosis, miR-33a expression in whole liver and serum samples was measured from chronic hepatitis B (CHB) patients by quantitative real-time PCR (qRT-PCR). Human and murine primary liver fibrosis-associated cells were isolated and treated with transforming growth factor-β1 (TGF-β1).
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