Dataset Information

New approaches for fibrosis regression in alcoholic cirrhosis.

ABSTRACT: Liver fibrosis is a dynamic process of fibrinogenesis and fibrinolysis. It is sequelae of recurrent injury and inflammation to the liver. Only recently has there been significant progress in understanding the pathophysiology behind liver fibrosis. This has allowed for the development of identifiable targets for potential therapies. In this article we will discuss the underlying general cellular mechanisms that play a key role in the pathway of fibrinogenesis and fibrinolysis and then focus on the mechanisms that are key in alcohol-induced liver fibrosis. Challenges in formulating potential fibrosis therapies as well as current potential targets for liver fibrosis will be reviewed as well.

SUBMITTER: Mehal W

PROVIDER: S-EPMC5602595 | biostudies-other | 2016 Sep

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

New approaches for fibrosis regression in alcoholic cirrhosis.

Mehal Wajahat W To Uyen U

Hepatology international 20160726 5

Liver fibrosis is a dynamic process of fibrinogenesis and fibrinolysis. It is sequelae of recurrent injury and inflammation to the liver. Only recently has there been significant progress in understanding the pathophysiology behind liver fibrosis. This has allowed for the development of identifiable targets for potential therapies. In this article we will discuss the underlying general cellular mechanisms that play a key role in the pathway of fibrinogenesis and fibrinolysis and then focus on th ...[more]

PMID: 27460408

Similar Datasets

Project description:BackgroundHepatic fibrosis is a widespread disease worldwide. Millions of people lose their lives due to hepatic fibrosis every year. The main causes of hepatic fibrosis include viral infection, alcoholism, and obesity. Many studies have been conducted on the single factors that cause hepatic fibrosis; however, no studies have examined whether hepatic fibrosis caused by multiple factors has concomitant expression molecules and signaling pathways. In this study, we sought to analyze the common differentially expressed messenger ribonucleic acids (mRNAs) of hepatic fibrosis caused by different factors, including hepatitis B virus (HBV) hepatic fibrosis, alcoholic hepatic fibrosis, and non-alcoholic hepatic fibrosis, and identify potential preventive and therapeutic targets.MethodsThe GSE171294, GSE142530, and GSE126848 datasets from the Gene Expression Omnibus (GEO) public database were used in this study. A |log fold change| >0.5 and a P value <0.05 were defined as differentially expressed mRNAs via R software screening. To further screen the target mRNAs, the differential mRNAs were subjected to a functional enrichment analysis based on the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Finally, the relationships between differentially expressed mRNA-encoded proteins were analyzed by a protein-protein interaction (PPI) analysis.ResultsA total of 54 differentially expressed mRNAs were identified. The KEGG analysis showed that the functions of different mRNAs mainly focused on Gonadotropin Releasing Hormone (GnRH) secretion, bile secretion and insulin secretion. The GO enrichment analysis showed that the differential mRNAs were mainly present in the cytoplasmic membrane region and exerted biological functions, such as activating channels and binding proteins by regulating biological processes (BPs), such as cells, cytoskeleton and heparin. The PPI network analysis revealed 16 nodes with 12 pairs of interactions. The 16 critical nodes included BCL6, CD4, CD24, IL32, CALD1, TRAF3, SOX9, KANSL3, MRGBP, PKD2, PKHD1, SYT1, ANXA4, KCNMA1, KCNN2, and CACNA1H.ConclusionsKCNN2, CD4, CD24, BCL6, KCNMA1, and other molecules obtained by the bioinformatics analysis of the RNA-sequencing data can be used as new research targets for hepatic fibrosis induced by different causes. Our findings could provide novel ideas for the treatment of hepatic fibrosis.

Project description:BackgroundThe risk of alcohol-related liver cirrhosis increases with increasing alcohol consumption, but many people with very high intake escape from liver disease. We postulate that susceptibility to alcoholic cirrhosis has a complex genetic component and propose that this can be dissected through a large and sufficiently powered genomewide association study (GWAS).MethodsThe GenomALC Consortium comprises researchers from Australia, France, Germany, Switzerland, United Kingdom, and United States, with a joint aim of exploring the genetic and genomic basis of alcoholic cirrhosis. For this National Institutes of Health/National Institute on Alcohol Abuse and Alcoholism funded study, we are recruiting high-risk drinkers who are either cases (with alcoholic cirrhosis) or controls (drinking comparable amounts over similar time, but free of significant liver disease). Extensive phenotypic data are obtained using semistructured interviews and patient records, and blood samples are collected.ResultsWe have successfully recruited 859 participants including 538 matched case-control samples as of September 2014, using study-specific inclusion-exclusion criteria and data collection protocols. Of these, 580 are cases (442 men and 138 women) and 279 are controls (205 men and 74 women). Duration of excessive drinking was slightly greater in cases than controls and was significantly less in women than men. Cases had significantly lower lifetime alcohol intake than controls. Both cases and controls had a high prevalence of reported parental alcohol problems, but cases were significantly more likely to report that a father with alcohol problems had died from liver disease (odds ratio 2.53, 95% confidence interval 1.31 to 4.87, p = 0.0055).ConclusionsRecruitment of participants for a GWAS of alcoholic cirrhosis has proved feasible across countries with multiple sites. Affected patients often consume less alcohol than unaffected ones, emphasizing the existence of individual vulnerability factors. Cases are more likely to report liver disease in a father with alcohol problems than controls, consistent with a potential genetic component to the risk of alcoholic cirrhosis.

Dataset Information

New approaches for fibrosis regression in alcoholic cirrhosis.

Publications

New approaches for fibrosis regression in alcoholic cirrhosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets