Document Detail


Intrahepatic expression of genes related to metabotropic receptors in chronic hepatitis.
MedLine Citation:
PMID:  22919248     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
AIM: To screen for genes related to metabotropic receptors that might be involved in the development of chronic hepatitis.
METHODS: Assessment of 20 genes associated with metabotropic receptors was performed in liver specimens obtained by punch biopsy from 12 patients with autoimmune and chronic hepatitis type B and C. For this purpose, a microarray with low integrity grade and with oligonucleotide DNA probes complementary to target transcripts was used. Evaluation of gene expression was performed in relation to transcript level, correlation between samples and grouping of clinical parameters used in chronic hepatitis assessment. Clinical markers of chronic hepatitis included alanine and aspartate aminotransferase, γ-glutamyltranspeptidase, alkaline phosphatase and cholinesterase activity, levels of iron ions, total cholesterol, triglycerides, albumin, glucose, hemoglobin, platelets, histological analysis of inflammatory and necrotic status, fibrosis according to METAVIR score, steatosis, as well as anthropometric body mass index, waist/hip index, percentage of adipose tissue and liver size in ultrasound examination. Gender, age, concomitant diseases and drugs were also taken into account. Validation of oligonucleotide microarray gene expression results was done with the use of quantitative real-time polymerase chain reaction (qRT-PCR).
RESULTS: The highest (0.002 < P < 0.046) expression among genes encoding main components of metabotropic receptor pathways, such as the α subunit of G-coupled protein, phosphoinositol-dependent protein kinase or arrestin was comparable to that of angiotensinogen synthesized in the liver. Carcinogenesis suppressor genes, such as chemokine ligand 4, transcription factor early growth response protein 1 and lysophosphatidic acid receptor, were characterized by the lowest expression (0.002 < P < 0.046), while the factor potentially triggering hepatic cancer, transcription factor JUN-B, had a 20-fold higher expression. The correlation between expression of genes of protein kinases PDPK1, phosphoinositide 3-kinase and protein kinase A (Spearman's coefficient range: 0.762-0.769) confirmed a functional link between these enzymes. Gender (P = 0.0046) and inflammation severity, measured by alanine aminotransferase activity (P = 0.035), were characterized by diverse metabotropic receptor gene expression patterns. The Pearson's coefficient ranging from -0.35 to 0.99 from the results of qRT-PCR and microarray indicated that qRT-PCR had certain limitations as a validation tool for oligonucleotide microarray studies.
CONCLUSION: A microarray-based analysis of hepatocyte metabotropic G-protein-related gene expression can reveal the molecular basis of chronic hepatitis.
Authors:
Andrzej Cieśla; Maciej Kuśmider; Agata Faron-Górecka; Marta Dziedzicka-Wasylewska; Monika Bociąga-Jasik; Danuta Owczarek; Irena Ciećko-Michalska; Dorota Cibor; Tomasz Mach
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  World journal of gastroenterology : WJG     Volume:  18     ISSN:  2219-2840     ISO Abbreviation:  World J. Gastroenterol.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-08-24     Completed Date:  2013-04-04     Revised Date:  2014-05-20    
Medline Journal Info:
Nlm Unique ID:  100883448     Medline TA:  World J Gastroenterol     Country:  China    
Other Details:
Languages:  eng     Pagination:  4156-61     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
3-Phosphoinositide-Dependent Protein Kinases
Adult
Arrestins / genetics,  metabolism
Biopsy
Female
GTP-Binding Protein alpha Subunits, Gs / genetics,  metabolism
Hepatitis B, Chronic / genetics,  metabolism*,  pathology
Hepatitis C, Chronic / genetics,  metabolism*,  pathology
Hepatocytes / metabolism,  pathology
Humans
Liver / metabolism*,  pathology
Male
Middle Aged
Oligonucleotide Array Sequence Analysis
Protein-Serine-Threonine Kinases / genetics,  metabolism
Receptors, G-Protein-Coupled / genetics*,  metabolism*
Retrospective Studies
Transcriptome*
Chemical
Reg. No./Substance:
0/Arrestins; 0/Receptors, G-Protein-Coupled; 0/beta-arrestin; EC 2.7.11.1/3-Phosphoinositide-Dependent Protein Kinases; EC 2.7.11.1/PDPK1 protein, human; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 3.6.1.-/GNAS protein, human; EC 3.6.5.1/GTP-Binding Protein alpha Subunits, Gs
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