scholarly journals Aquaporin 9 Represents a Novel Target of Chronic Liver Injury That May Antagonize Its Progression by Reducing Lipotoxicity

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Quancheng Cheng ◽  
Huiru Ding ◽  
Jinyu Fang ◽  
Xuan Fang ◽  
Huaicun Liu ◽  
...  
Keyword(s):  
Liver Injury ◽  
Molecular Mechanisms ◽  
Gene Knockout ◽  
Clinical Manifestations ◽  
Chronic Liver ◽  
Common Disease ◽  
Chronic Liver Injury ◽  
Aquaporin 9 ◽  
Hepatic Lipotoxicity ◽  
Novel Target

In recent years, chronic liver injury has become a common disease that harms human health. Its clinical manifestations are hepatic steatosis and secondary chronic steatohepatitis, which can quickly transform into liver fibrosis and cirrhosis if not treated in time. Therefore, this study is aimed at searching for new therapeutic targets of chronic liver injury and clarifying the molecular mechanisms of the new targets involved in chronic liver injury. After aquaporin 9 was identified as a target by proteomics, Aqp9-/- mice were constructed using the CRISPR/Cas9 system. Biochemical and morphological tests were used to verify the effect of Aqp9 knockout on early chronic liver injury. Proteomics, molecular biology, and morphology experiments were used to screen and verify the effects of Aqp9 knockout on its downstream pathway. Through the above experiments, we demonstrated that aquaporin 9 could be used as an intervention target for antagonizing the development of early chronic liver injury and its gene knockout affected downstream inflammation, oxidative stress, apoptosis, and pyroptosis by alleviating hepatic lipotoxicity.

scholarly journals Target prediction of anti-chronic liver injury of Kangxian pill based on network pharmacology

2021 ◽  
Author(s):  
Min Cao ◽  
Yiyang Wang ◽  
Haizhao Liu ◽  
Xueqian Dong ◽  
Mengxue Dong ◽  
...  
Keyword(s):  
Liver Injury ◽  
Protein Expression ◽  
Molecular Mechanisms ◽  
Target Prediction ◽  
Vital Role ◽  
Chronic Liver ◽  
Network Pharmacology ◽  
Chronic Liver Injury ◽  
Tnf Α

Abstract BackgroundThe present study aimed to validate the protect effect of Kangxian pill (KXP) on chronic hepatic injury (CHI) and investigate its potential mechanism by network pharmacology-based prediction and experimental verification in vivo . MethodsThe effect of KXP in the treatment of carbon tetrachloride (CCL 4 )-induced CHI is investigated by calculating liver index, measuring AST and ALT levels and performing HE staining. Targets of active ingredients of KXP were predicted in TCSMP and targets of chronic liver injury were searched in DisGeNET, OMIM and GeneCards databases. We obtain some pivotal targets of KXP for the treatment of CHI by intersecting the targets of KXP and CHI. Subsequently, we performed gene ontology (GO) functional and pathways enrichment analyses, as well as conducted networks based on potential targets to determine the core targets and representative pathways.We further validated expressions of IL-6, IL-1β, TNF-α, Bax, Bcl2, PI3K, Akt, and pAkt according to the potential molecular mechanisms analyzed based on network pharmacology analysis.ResultsThe results showed that the levels of AST and ALT in serum decreased after treatment with KXP. HE staining also revealed that KXP could improve hepatocyte abnormality in vivo . A total of 81 potential targets of KXP in the treatment of CHI were identified through network pharmacology analysis. After integrating potential targets, function enrichment, representative pathways and networks, we identified PI3K, AKT1,BCL2, TNF-α, IL-1β, and IL-6 as potential targets, which may play a vital role in the KXP treatment. The experimental results also showed that KXP could down-regulate the mRNA and protein expression of IL-1β, IL-6, TNF-α and Bax, and up-regulate the PI3K and p-Akt protein expression i n vivo .ConclusionsOur results suggest that KXP could alleviate CHI through regulating inflammation and apoptosis and provide deep insight into the hepato-protective mechanisms.

Ductular reactions provide a structural biliary network to preserve bile drainage in the CDE-model of hepatocellular chronic liver injury

2017 ◽  
Vol 66 (1) ◽  
pp. S6
Author(s):  
L.-A. Clerbaux ◽  
R. Manco ◽  
N. Van Hul ◽  
R. Español-Suñer ◽  
C. Bouzin ◽  
...  
Keyword(s):  
Liver Injury ◽  
Chronic Liver ◽  
Chronic Liver Injury ◽  
Bile Drainage

Gab1 in livers with persistent hepatocyte apoptosis has an antiapoptotic effect and reduces chronic liver injury, fibrosis and tumorigenesis

2021 ◽  
Author(s):  
Tetsuo Takehara ◽  
Naoki Mizutani ◽  
Hayato Hikita ◽  
Yoshinobu Saito ◽  
Yuta Myojin ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Liver Injury ◽  
Cell Viability ◽  
Liver Regeneration ◽  
Adaptor Protein ◽  
Chronic Liver ◽  
Hepatocyte Apoptosis ◽  
Chronic Liver Injury ◽  
The Impact

Grb2-associated binder 1 (Gab1) is an adaptor protein that is important for intracellular signal transduction by receptor tyrosine kinases that are receptors for various growth factors and plays an important role in rapid liver regeneration after partial hepatectomy and during acute hepatitis. On the other hand, mild liver regeneration is induced in livers of individuals with chronic hepatitis, where hepatocyte apoptosis is persistent; however, the impact of Gab1 on such livers remains unclear. We examined the role of Gab1 in chronic hepatitis. Gab1 knockdown enhanced the decrease in cell viability and apoptosis induced by ABT-737, a Bcl-2/-xL/-w inhibitor, in BNL.CL2 cells, while cell viability and caspase activity were unchanged in the absence of ABT-737. ABT-737 treatment induced Gab1 cleavage to form p35-Gab1. p35-Gab1 was also detected in the livers of mice with hepatocyte-specific Mcl-1 knockout (KO), which causes persistent hepatocyte apoptosis. Gab1 deficiency exacerbated hepatocyte apoptosis in Mcl-1 KO mice with posttranscriptional downregulation of Bcl-XL. In BNL.CL2 cells treated with ABT-737, Gab1 knockdown posttranscriptionally suppressed Bcl-xL expression, and p35-Gab1 overexpression enhanced Bcl-xL expression. Gab1 deficiency in Mcl-1 KO mice activated STAT3 signaling in hepatocytes, increased hepatocyte proliferation, and increased the incidence of liver cancer with the exacerbation of liver fibrosis. In conclusion, Gab1 is cleaved in the presence of apoptotic stimuli and forms p35-Gab1 in hepatocytes. In chronic liver injury, the role of Gab1 in suppressing apoptosis and reducing liver damage, fibrosis, and tumorigenesis is more important than its role in liver regeneration.

scholarly journals CD248/endosialin critically regulates hepatic stellate cell proliferation during chronic liver injury via a PDGF-regulated mechanism

Gut ◽  
2015 ◽  
Vol 65 (7) ◽  
pp. 1175-1185 ◽  
Author(s):  
Annika Wilhelm ◽  
Victoria Aldridge ◽  
Debashis Haldar ◽  
Amy J Naylor ◽  
Christopher J Weston ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Liver Injury ◽  
Hepatic Stellate Cell ◽  
Stellate Cell ◽  
Chronic Liver ◽  
Chronic Liver Injury

Extracellular vesicles derived from human embryonic stem cell‐MSCs ameliorate cirrhosis in thioacetamide‐induced chronic liver injury

2018 ◽  
Vol 233 (12) ◽  
pp. 9330-9344 ◽  
Author(s):  
Soura Mardpour ◽  
Seyedeh‐Nafiseh Hassani ◽  
Saeid Mardpour ◽  
Forough Sayahpour ◽  
Massoud Vosough ◽  
...  
Keyword(s):  
Stem Cell ◽  
Liver Injury ◽  
Embryonic Stem Cell ◽  
Extracellular Vesicles ◽  
Human Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Chronic Liver ◽  
Chronic Liver Injury

scholarly journals HMGB1 links chronic liver injury to progenitor responses and hepatocarcinogenesis

2018 ◽  
Vol 128 (6) ◽  
pp. 2436-2451 ◽  
Author(s):  
Celine Hernandez ◽  
Peter Huebener ◽  
Jean-Philippe Pradere ◽  
Daniel J. Antoine ◽  
Richard A. Friedman ◽  
...  
Keyword(s):  
Liver Injury ◽  
Chronic Liver ◽  
Chronic Liver Injury
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