Abstract
To determine the effects ofanthocyanins from blueberries on hepatic stellate cell (HSCs-T6) and on histone acetylation during liver fibrosis induced by CCl4 in rats. Fifty male SD rats weighing 180 ± 20g were randomly placed into a control group, a hepatic fibrosis group, a blueberry treatment group, a blueberry intervention group, and a natural recovery group. After the rats were sacrificed, the livers and the liver indexes were measured, and the pathological changes were observed by HE staining and Masson staining. The blood was analyzed for the four indexes of liver fibrosis and liver function; nucleoprotein from liver tissues and karyoplasm were isolated to determine the expression of acH3K9, acH3K14, and acH3K18 by Western blotting.Compared with the lethal rate of the control group, the median lethal rate of HSCs-T6 cells treated with a the 50μmol/L concentration was 66.94% (P < 0.05). The protein expression on α-SMA, type I collagen, TIMP1 significantly decreased (P < 0.05) following treatment with 50 ug/ml of anthocyanin for 36 h; moreover, the expression of acH3K9, acH3K14 and acH3K18 modification were up-regulated (P < 0.05). Furthermore, compared with the liver in the model group, the liver in the intervention group showed the most obvious improvement (P < 0.01), and its karyoplasm had increased expression of acH3K9, acH3K14 and acH3K18 (P<0.01).Regulating histone acetylation could improve liver function and liver fibrosis indexes in rats with hepatic fibrosis. The mechanism might be related to certain genes that promote apoptosis, so as to inhibit the effect of anti hepatic fibrosis.
Highlights
It has been reported that histone acetylation may play a role in the development of hepatic fibrosis; the mechanism through which histone acetylation leads to the development and progression of hepatic fibrosis is unknown
To determine the effects ofanthocyanins from blueberries on hepatic stellate cell (HSCs-T6) and on histone acetylation during liver fibrosis induced by CCl4 in rats
It has been reported that blueberries can improve liver fibrosis through cell apoptosis; so what changes does histone acetylation undergo during the development of liver fibrosis? How does the level of histone acetylation change in www.impactjournals.com/oncotarget the body and liver of blueberry-treated animals in vitro and in vitro? To answer these questions, we explored the effect of the anthocyanins in blueberries on the apoptosis of rat hepatic stellate cell lines (HSCs-T6), and the modification of acH3K9, acH3K14, and acH3K18 loci in this study; further, the effects of blueberries on liver function, hepatic fibrosis, and the histone acetylation of acH3K9, acH3K14, and acH3K18 were investigated in rats after liver fibrosis induced by carbon tetrachloride (CCl4)
Summary
It has been reported that histone acetylation may play a role in the development of hepatic fibrosis; the mechanism through which histone acetylation leads to the development and progression of hepatic fibrosis is unknown. It has been reported that blueberries can improve liver fibrosis through cell apoptosis; so what changes does histone acetylation undergo during the development of liver fibrosis? We explored the effect of the anthocyanins in blueberries on the apoptosis of rat hepatic stellate cell lines (HSCs-T6), and the modification of acH3K9, acH3K14, and acH3K18 loci in this study; further, the effects of blueberries on liver function, hepatic fibrosis, and the histone acetylation of acH3K9, acH3K14, and acH3K18 were investigated in rats after liver fibrosis induced by carbon tetrachloride (CCl4). We observed the effect of the anthocyanins in blueberry on the cellular model in vitro and CCl4-induced liver fibrosis in the rat histone acetylation modification model, and provided a reference for the experiment
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