机构地区:[1]Department of Gastroenterology,Hepatology and Infectious Diseases,Jagiellonian University Medical College,31-521 Kraków,Poland [2]Institute of Pharmacology,Polish Academy of Sciences,31-343 Kraków,Poland
出 处:《World Journal of Gastroenterology》2012年第31期4156-4161,共6页世界胃肠病学杂志(英文版)
摘 要:AIM: To screen for genes related to metabotropic re- ceptors that might be involved in the development of chronic hepatitis. METHODS: Assessment of 20 genes associated with metabotropic receptors was performed in liver speci- mens 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. Clini- cal markers of chronic hepatitis included alanine and aspartate aminotransferase, ~,-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 adi- pose 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) expres- sion among genes encoding main components of metabotropic receptor pathways, such as the a subunit of G-coupled protein, phosphoinositol-dependent pro- tein kinase or arrestin was comparable to that of an- giotensinogen synthesized in the liver. Carcinogenesis suppressor genes, such as chemokine ligand 4, tran- scription 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, transcrip- tion factor JUN-B, had a 20-fold higher expression. The correlation betweenAIM: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,-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 kin
关 键 词:Metabotropic receptors Gene expression DNA oligonucleotides Quantitative real-time poly-merase chain reaction Chronic hepatitis
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