AIM:To reveal the functions of micro RNAs(mi RNAs) with respect to hepatic stellate cells(HSCs) in response to portal hypertension.METHODS:Primary rat HSCs were exposed to static water pressure(10 mm Hg,1 h) and the p...AIM:To reveal the functions of micro RNAs(mi RNAs) with respect to hepatic stellate cells(HSCs) in response to portal hypertension.METHODS:Primary rat HSCs were exposed to static water pressure(10 mm Hg,1 h) and the pressureinduced mi RNA expression profile was detected by next-generation sequencing. Quantitative real-time polymerase chain reaction was used to verify the expression of mi RNAs. A potential target of Mi R-9a-5p was measured by a luciferase reporter assay and Western blot. CCK-8 assay and Transwell assay were used to detect the proliferation and migration of HSCs under pressure.RESULTS:According to the profile,the expression of mi R-9a-5p was further confirmed to be significantly increased after pressure overload in HSCs(3.70 ± 0.61 vs 0.97 ± 0.15,P = 0.0226),which resulted in the proliferation,migration and activation of HSCs. In vivo,the up-regulation of mi R-9a-5p(2.09 ± 0.91 vs 4.27 ± 1.74,P = 0.0025) and the down-regulation of Sirt1(2.41 ± 0.51 vs 1.13 ± 0.11,P = 0.0006) were observed in rat fibrotic liver with portal hypertension. Sirt1 was a potential target gene of mi R-9a-5p. Through restoringthe expression of Sirt1 in mi R-9a-5p transfected HSCs on pressure overload,we found that overexpression of Sirt1 could partially abrogate the mi R-9a-5p mediated suppression of the proliferation,migration and activation of HSCs. CONCLUSION:Our results suggest that during liver fibrosis,portal hypertension may induce the proliferation,migration and activation of HSCs through the up-regulation of mi R-9a-5p,which targets Sirt1.展开更多
The mechanism of health effects caused by organohalogen pollutants, e.g., toxins from electronic waste(e-waste), is poorly understood. We supposed that micro RNAs(mi RNAs), an important post-transcriptional regulator,...The mechanism of health effects caused by organohalogen pollutants, e.g., toxins from electronic waste(e-waste), is poorly understood. We supposed that micro RNAs(mi RNAs), an important post-transcriptional regulator, could play a role in this process. In this study, fasting peripheral blood samples were collected from residents living at an e-waste site in northern China and a nearby reference population. Concentrations of e-waste related organohalogen pollutants in plasma from the exposure group were higher than the corresponding measurement in the reference group. Correspondingly, sixty mi RNAs in plasma showed > 2-fold change between the two groups in microarray analysis. Among them, mi R-125a-5p was confirmed to be upregulated by q RT-PCR and its validated targets were enriched in responses to xenobiotics and cancer related pathways. Furthermore, significant positive correlations were found between levels of mi R-125a-5p in plasma and reactive oxygen species(ROS) in polymorphonuclear neutrophil leukocytes(P < 0.05). These evidences suggested oxidative stress might be an intermediate between e-waste related POPs exposure and alteration of plasma mi RNA.展开更多
基金Supported by National Natural Science Foundation of China,No.11272342/A0205
文摘AIM:To reveal the functions of micro RNAs(mi RNAs) with respect to hepatic stellate cells(HSCs) in response to portal hypertension.METHODS:Primary rat HSCs were exposed to static water pressure(10 mm Hg,1 h) and the pressureinduced mi RNA expression profile was detected by next-generation sequencing. Quantitative real-time polymerase chain reaction was used to verify the expression of mi RNAs. A potential target of Mi R-9a-5p was measured by a luciferase reporter assay and Western blot. CCK-8 assay and Transwell assay were used to detect the proliferation and migration of HSCs under pressure.RESULTS:According to the profile,the expression of mi R-9a-5p was further confirmed to be significantly increased after pressure overload in HSCs(3.70 ± 0.61 vs 0.97 ± 0.15,P = 0.0226),which resulted in the proliferation,migration and activation of HSCs. In vivo,the up-regulation of mi R-9a-5p(2.09 ± 0.91 vs 4.27 ± 1.74,P = 0.0025) and the down-regulation of Sirt1(2.41 ± 0.51 vs 1.13 ± 0.11,P = 0.0006) were observed in rat fibrotic liver with portal hypertension. Sirt1 was a potential target gene of mi R-9a-5p. Through restoringthe expression of Sirt1 in mi R-9a-5p transfected HSCs on pressure overload,we found that overexpression of Sirt1 could partially abrogate the mi R-9a-5p mediated suppression of the proliferation,migration and activation of HSCs. CONCLUSION:Our results suggest that during liver fibrosis,portal hypertension may induce the proliferation,migration and activation of HSCs through the up-regulation of mi R-9a-5p,which targets Sirt1.
基金National Natural Science Foundation of China(21322705,41121004,21190051,and 21177091)
文摘The mechanism of health effects caused by organohalogen pollutants, e.g., toxins from electronic waste(e-waste), is poorly understood. We supposed that micro RNAs(mi RNAs), an important post-transcriptional regulator, could play a role in this process. In this study, fasting peripheral blood samples were collected from residents living at an e-waste site in northern China and a nearby reference population. Concentrations of e-waste related organohalogen pollutants in plasma from the exposure group were higher than the corresponding measurement in the reference group. Correspondingly, sixty mi RNAs in plasma showed > 2-fold change between the two groups in microarray analysis. Among them, mi R-125a-5p was confirmed to be upregulated by q RT-PCR and its validated targets were enriched in responses to xenobiotics and cancer related pathways. Furthermore, significant positive correlations were found between levels of mi R-125a-5p in plasma and reactive oxygen species(ROS) in polymorphonuclear neutrophil leukocytes(P < 0.05). These evidences suggested oxidative stress might be an intermediate between e-waste related POPs exposure and alteration of plasma mi RNA.
