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The Role of Tec Kinase Signaling Pathways in the Development of Mallory Denk Bodies in balloon cells in Alcoholic Hepatitis
- Publication Year :
- 2017
-
Abstract
- Several research strategies have been used to study the pathogenesis of alcoholic hepatitis (AH). These strategies have shown that various signaling pathways are the target of alcohol in liver cells. However, few have provided specific mechanisms associated with Mallory-Denk Bodies (MDBs) formed in Balloon cells in AH. The formation of MDBs in these hepatocytes is an indication that the mechanisms of protein quality control have failed. The MDB is the result of aggregation and accumulation of proteins in the cytoplasm of balloon degenerated liver cells. To understand the mechanisms that failed to degrade and remove proteins in the hepatocyte from patients suffering from alcoholic hepatitis, we investigated the pathways that showed significant up regulation in the AH liver biopsies compared to normal control livers. (Liu et al., 2015). Analysis of genomic profiles of AH liver biopsies and control livers by RNA-seq revealed different pathways that were up regulated significantly. In this study, the focus was on Tec kinase signaling pathways and the genes that significantly interrupt this pathway. Quantitative PCR and immunofluorescence staining results, indicated that several genes and proteins are significantly over expressed in the livers of AH patients that affect the Tec kinase signaling to PI3K which leads to activation of Akt and its downstream effectors.
- Subjects :
- 0301 basic medicine
Clinical Biochemistry
Alcoholic hepatitis
Biology
Mallory Bodies
Article
Pathology and Forensic Medicine
03 medical and health sciences
0302 clinical medicine
Downregulation and upregulation
medicine
Mallory body
Humans
Molecular Biology
Protein kinase B
PI3K/AKT/mTOR pathway
Hepatitis, Alcoholic
Gene Expression Profiling
High-Throughput Nucleotide Sequencing
Protein-Tyrosine Kinases
medicine.disease
Cell biology
030104 developmental biology
medicine.anatomical_structure
Liver
Cytoplasm
030220 oncology & carcinogenesis
Hepatocyte
Case-Control Studies
Cancer research
Hepatocytes
Signal transduction
Biomarkers
Signal Transduction
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....a2aea2eb0d31bcf4d6f08219913b8768