scholarly journals The Transforming Growth Factor β1/Interleukin-31 Pathway Is Upregulated in Patients with Hepatitis B Virus-Related Acute-on-Chronic Liver Failure and Is Associated with Disease Severity and Survival

2015 ◽  
Vol 22 (5) ◽  
pp. 484-492 ◽  
Author(s):  
Xueping Yu ◽  
Ruyi Guo ◽  
Desong Ming ◽  
Yong Deng ◽  
Milong Su ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Liver Injury ◽  
Hepatitis B ◽  
Disease Severity ◽  
Transforming Growth Factor ◽  
Serum Levels ◽  
Transforming Growth Factor Β1 ◽  
Chronic Liver Failure ◽  
B Virus ◽  
Tgf Β1

ABSTRACTThe transforming growth factor β1/interleukin-31 (TGF-β1/IL-31) pathway plays an important role in the process of cell injury and inflammation. The purpose of this work was to explore the role of the TGF-β1/IL-31 pathway in the cytopathic process of hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF). The quantitative serum levels of TGF-β1, IL-9, IL-10, IL-17, IL-22, IL-23, IL-31, IL-33, and IL-35 were analyzed among chronic hepatitis B (CHB) patients (n= 17), ACLF patients (n= 18), and normal control (NC) subjects (n= 18). Disease severity in patients with ACLF was assessed using the model for end-stage liver disease (MELD) and Child-Pugh scores. Serum TGF-β1 levels were strongly positively correlated with IL-31 in all subjects, and both of them were positively correlated with IL-17, IL-22, and IL-33. In CHB and ACLF patients, serum levels of TGF-β1 and IL-31 were both increased significantly compared with those in NC subjects and positively correlated with total bilirubin (TBil) and alpha-fetoprotein (AFP) levels. ACLF patients showed the highest levels of TGF-β1 and IL-31, which were positively correlated with Child-Pugh scores. Furthermore, the recovery from the liver injury in CHB was accompanied by decreased TGF-β1 and IL-31 levels. More importantly, serum levels of TGF-β1 and IL-31 were markedly upregulated in ACLF nonsurvivors, and IL-31 displayed the highest sensitivity and specificity (85.7% and 100.0%, respectively) in predicting nonsurvival of ACLF patients. Increasing activity of the TGF-β1/IL-31 pathway is well correlated with the extent of liver injury, disease severity, and nonsurvival of ACLF patients, while reducing activity is detected along the recovery from liver injury in CHB, suggesting its potential role in the pathogenesis of liver injury during chronic HBV infection.

scholarly journals Hepatitis B virus X antigen promotes transforming growth factor-β1 (TGF-β1) activity by up-regulation of TGF-β1 and down-regulation of α 2-macroglobulin

2004 ◽  
Vol 85 (2) ◽  
pp. 275-282 ◽  
Author(s):  
Jingbo Pan ◽  
Marcy Clayton ◽  
Mark A. Feitelson
Keyword(s):  
Hepatitis B Virus ◽  
Growth Factor ◽  
Hepatitis B ◽  
Target Genes ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Sensitive Cell Line ◽  
Cdna Subtraction ◽  
B Virus ◽  
Tgf Β1

Hepatitis B virus (HBV) X antigen (HBxAg) may contribute to the development of hepatocellular carcinoma (HCC) by activation of signalling pathways such as NF-κB. To identify NF-κB target genes differentially expressed in HBxAg-positive compared to -negative cells, HepG2 cells consistently expressing HBxAg (HepG2X cells) were stably transfected with pZeoSV2 or pZeoSV2-IκBα. mRNA from each culture was isolated and compared by PCR select cDNA subtraction. The results showed lower levels of α 2-macroglobulin (α 2-M) in HepG2X-pZeoSV2 compared to HepG2X-pZeoSV2-IκBα cells. This was confirmed by Northern and Western blotting, and by measurement of extracellular α 2-M levels. Elevated transforming growth factor-β1 (TGF-β1) levels were also seen in HepG2X compared to control cells. Serum-free conditioned medium (SFCM) from HepG2X cells suppressed DNA synthesis in a TGF-β-sensitive cell line, Mv1Lu. The latter was reversed when the SFCM was pretreated with exogenous, activated α 2-M or with anti-TGF-β. Since elevated TGF-β1 promotes the development of many tumour types, these observations suggest that the HBxAg-mediated alteration in TGF-β1 and α 2-M production may contribute importantly to the pathogenesis of HCC.

KCTD9 contributes to liver injury through NK cell activation during hepatitis B virus-induced acute-on-chronic liver failure

2013 ◽  
Vol 146 (3) ◽  
pp. 207-216 ◽  
Author(s):  
Tao Chen ◽  
Lin Zhu ◽  
Yaoyong Zhou ◽  
Bin Pi ◽  
Xiaojuan Liu ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Liver Injury ◽  
Hepatitis B ◽  
Liver Failure ◽  
Cell Activation ◽  
Nk Cell ◽  
Chronic Liver ◽  
Chronic Liver Failure ◽  
B Virus

Elevated TGF-β1/IL-31 Pathway Is Associated with the Disease Severity of Hepatitis B Virus–Related Liver Cirrhosis

2015 ◽  
Vol 28 (4) ◽  
pp. 209-216 ◽  
Author(s):  
Desong Ming ◽  
Xueping Yu ◽  
Ruyi Guo ◽  
Yong Deng ◽  
Julan Li ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Disease Severity ◽  
B Virus ◽  
Tgf Β1

scholarly journals Transforming growth factor-β1 suppresses hepatitis B virus replication primarily through transcriptional inhibition of pregenomic RNA

Hepatology ◽  
2007 ◽  
Vol 46 (3) ◽  
pp. 672-681 ◽  
Author(s):  
Yu-Chi Chou ◽  
Mong-Liang Chen ◽  
Cheng-Po Hu ◽  
Ya-Ling Chen ◽  
Chin-Liew Chong ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Growth Factor ◽  
Hepatitis B ◽  
Virus Replication ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Transcriptional Inhibition ◽  
B Virus

scholarly journals TGF-β1 accelerates the hepatitis B virus X-induced malignant transformation of hepatic progenitor cells by upregulating miR-199a-3p

Oncogene ◽  
2019 ◽  
Vol 39 (8) ◽  
pp. 1807-1820 ◽  
Author(s):  
Ke-shuai Dong ◽  
Yan Chen ◽  
Guang Yang ◽  
Zhi-bin Liao ◽  
Hong-wei Zhang ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Liver Cancer ◽  
Hepatitis B ◽  
Progenitor Cells ◽  
Malignant Transformation ◽  
Transforming Growth Factor ◽  
Hepatic Progenitor Cells ◽  
B Virus ◽  
Mesenchymal Transformation ◽  
Tgf Β1

AbstractIncreasing evidence has suggested that liver cancer arises partially from transformed hepatic progenitor cells (HPCs). However, the detailed mechanisms underlying HPC transformation are poorly understood. In this study, we provide evidence linking the coexistence of hepatitis B virus X protein (HBx) and transforming growth factor beta 1 (TGF-β1) with miR-199a-3p in the malignant transformation of HPCs. The examination of liver cancer specimens demonstrated that HBx and TGF-β1 expression was positively correlated with epithelial cell adhesion molecule (EpCAM) and cluster of differentiation 90 (CD90). Importantly, EpCAM and CD90 expression was much higher in the specimens expressing both high HBx and high TGF-β1 than in those with high HBx or high TGF-β1 and the double-low-expression group. HBx and TGF-β1 double-high expression was significantly associated with poor prognosis in primary liver cancer. We also found that HBx and TGF-β1 induced the transformation of HPCs into hepatic cancer stem cells and promoted epithelial–mesenchymal transformation, which was further enhanced by concomitant HBx and TGF-β1 exposure. Moreover, activation of the c-Jun N-terminal kinase (JNK)/c-Jun pathway was involved in the malignant transformation of HPCs. miR-199a-3p was identified as a significantly upregulated microRNA in HPCs upon HBx and TGF-β1 exposure, which were shown to promote miR-199a-3p expression via c-Jun-mediated activation. Finally, we found that miR-199a-3p was responsible for the malignant transformation of HPCs. In conclusion, our results provide evidence that TGF-β1 cooperates with HBx to promote the malignant transformation of HPCs through a JNK/c-Jun/miR-199a-3p-dependent pathway. This may open new avenues for therapeutic interventions targeting the malignant transformation of HPCs in treating liver cancer.

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