Chinese Hepatolgy

Revealing role of miRNA in the pathogenesis of liver fibrosis by integrated bioinformatics analysis

HUANG Chong, ZHENG Ya-hui, ZHANG Ju-bo

2019, 24(12): 1381-1386.

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Objective To reveal the potential role of micro-ribonucleic acid (microRNA) in the pathogenesis of liver fibrosis.Methods MicroRNA microarray GSE19865 and GSE66278 were downloaded from gene expression omnibus (GEO) database. The data was analyzed with GEO2R. The microRNAs up-regulated in both microarrays were analyzed by TargetScan and microT-CDS for target gene prediction, and target genes predicted by both were further subjected to functional analysis. Results In GSE19865, 37 microRNAs were up-regulated, and none was down-regulated. While in GSE66278, 19 microRNAs were up-regulated and 18 microRNAs were down-regulated. The miR-802 was upregulated both in GSE19865 and GSE66278. A total of 138 candidate target genes were predicted by both TargetScan and microT-CDS. Functional analysis revealed that mainly function of these genes were participated in pathways and biological processes like mitochondrial biogenesis, transforming growth factor-beta signaling pathway, histone lysine methylation, Wnt/Ca²⁺ pathway, etc. Protein-protein interaction analysis identified YWHAE, PPP2CA, RHOA, FOS, PSMD2, CDK19, ATF2 and PAFAH1B1 as hub genes.Conclusion By integrated bioinformatics analysis, miR-802 is involved in the liver fibrosis. Mechanistically, miR-802 regulates biological processes including histone methylation by targeting genes like YWHAE, PPP2CA and RHOA.

5-HT inhibits actinomycin D induced hepatocyte apoptosis by upregulating 2B receptor

MA Li-xia, GAO Yu-juan, LIU Xiao-hui, ZHANG Jing

2019, 24(12): 1387-1392.

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Objective To investigate the role and mechanism of 5-hydroxytryptamine (5-HT) in hepatocyte apoptosis, and to provide evidence for the application of 5-HT in liver diseases.Methods Apoptosis of HepG2 and 7702 cells was induced by different concentrations of actinomycin-D (AcD). After AcD pretreatment of HepG2 cells, 5-HT, 5-HT 2A receptor agonist DOI, 5-HT 2B receptor agonist M110, and 5-HT 2B receptor antagonist SB204 with 5-HT were added respectively. Then, apoptotic rates and survival rates were detected by Annexin V-FITC/PI flow cytometry and MTT assay, expressions of aspartate specific protease 3 (caspase-3), serine/threonine protein kinase (AKT) and phosphorylated serine/threonine protein kinase (p-AKT) were detected by Western blot method. Results AcD induced apoptosis of HepG2 cells and 7702 cells in a concentration-dependent manner. The apoptotic rates of cells treated with 50 ng/ml AcD were higher than those of serum-free control group (HepG2 cells t=1.71, 7702 cells t=1.98, P<0.05). Compared with the AcD group, 5-HT decreased the apoptosis rate of HepG2 cells from 31.96% ± 2.13% to 10.24% ± 2.59% (t=1.62, P<0.05), and the 5-HT 2B receptor agonist decreased the apoptosis rate to 8.41% ± 0.96% (t=1.75, P<0.05). On the contrary, the 5-HT 2B receptor antagonist antagonize the anti-apoptotic effect of 5-HT, making the apoptotic rate 25.92% ± 1.33% (t=1.45, P>0.05). Both 5-HT and 5-HT 2B receptor agonists reduced the activation of caspase3, increased the phosphorylation of AKT, and decreased the apoptosis.Conclusion 5-HT promotes AKT phosphorylation by up-regulating 5-HT 2B receptor, thereby inhibiting AcD-induced hepatocyte apoptosis.

Mechanism of LncRNA NEAT1 deficiency aggravating acetaminophen-induced acute liver injury

ZHAO Jie, ZHONG Cheng-peng, CAI Jie, ZHANG Jian-jun

2019, 24(12): 1393-1395.

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Objective The aim of this study was to investigate the molecular role of long non-coding ribonucleic acid (lncRNA) nuclear enriched abundant transcript 1 (NEAT1) in the pathogenesis of acetaminophen (APAP)-induced acute liver injury.Methods In our study, 8 C57BL/6 mice were randomly divided into experimental group and control group, with 4 mice in each group. Acute liver injury was induced by intraperitoneal injection of APAP. The mouse liver tissue RNA was extracted to detect the expression of lncRNA NEAT1. Mouse primary hepatocytes were extracted and cultured. In experimental group, hepatocytes were treated with small interfering ribonucleic acid (siRNA) to knock down lncRNA NEAT1, and then stimulated with APAP. The expression of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in cell culture supernatant is dectected to evaluate the degree of damage, together with histological analysis. Results In vivo, ALT (7565 ± 763.3 vs 42.75 ± 2.3, P<0.05) and AST (7718 ± 901.6 vs 45.05 ± 4.1, P<0.05) were significantly higher in the APAP-treated group than control group. The expression of lncRNA NEAT1 in liver tissues of the APAP-treated group was 3 times higher than that of control group (P<0.05). In vitro experiments, lncRNA NEAT1 expression was significantly increased after APAP stimulation in primary hepatocyte medium for 24 hours. ALT and AST in the supernatant of hepatocytes in the experimental group treated by siRNA and APAP were significantly higher than those in control group.Conclusion Our results indicate that knockdown of lncRNA NEAT1 can exacerbate APAP-induced acute liver injury, suggesting the potential benefit of lncRNA NEAT1 in the prevention and treatment of APAP-induced acute liver injury in the clinic.

Clinicopathological features and treatment of autoimmune hepatitis in childhood

Gulinuer Saitihan, Hanipa Simayi

2019, 24(12): 1396-1398.

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Objective To investigate the clinicopathological features and therapies of autoimmune hepatitis (AIH) in childhood.Methods Clinical data of 82 children with AIH who were treated in our hospital from January 2017 to December 2018 were retrospectively analyzed. The children were divided into AIH type I group and AIH type II group according to the classification criteria. The clinical data of patients were collected from hospital information management system, and the differences in pathogenesis, biochemical indicators, clinical manifestations, therapeutic effects and pathological characteristics between the 2 groups were analyzed. Results The total bilirubin of AIH type I group was 52.16 ± 15.21 μmol/L, which was significantly lower than that of AIH type II group (97.64 ± 18.40 μmol/L). The immunoglobulin G of AIH type I group was 27.69 ± 3.47 g/L, which was significantly higher than that of AIH Type II group (18.25 ± 2.14 g/L). And the differences were statistically significant (P < 0.05). The infiltration ratio of lymphocytes or plasma cells in AIH type I group was 79.31%, which was significantly higher than that in AIH type II group of 16.67%. The composition ratio of interface hepatitis in AIH type I group was 17.24%, which was significantly lower than that in AIH type II group of 79.17%. And the differences were statistically significant (P<0.05). There were 12 cases of completely remission (CR) and 29 cases of partial remission (PR) in AIH type I group, 5 cases of CR and 11 cases of PR in AIH type II group. The effective rate was 70.69% in type I group, 66.67% in type II group, and the difference between the 2 groups was not statistically significant (P>0.05).Conclusion The incidence of AIH type I in childhood was higher than that of type II, and the biochemical parameters and pathological characteristics of children with different types of AIH were significantly different. The infiltration of lymphocytes or plasma cells, and interface hepatitis were relatively serious in children. After treatment, the curative effect was significant, with no significant difference in different types.

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