Multiple inflammatory-, tissue remodelling- and fibrosis genes are differentially transcribed in the livers ofAbcb4(−/ − ) mice harbouring chronic cholangitis
| Autor: | Annlaug Ødegaard, K. Arnkværn, Terese Haaland, Morten G. Ræder, Knut Jørgen Labori, Knut Erik Berge, Ståle Nygård, Karl Esten Nakken |
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| Rok vydání: | 2007 |
| Předmět: |
Pathology
medicine.medical_specialty Chemokine ATP Binding Cassette Transporter Subfamily B Transcription Genetic Microarray Cholangitis Mice Inbred Strains Biology Polymerase Chain Reaction Mice Fibrosis medicine Animals CXCL10 Gene Oligonucleotide Array Sequence Analysis Inflammation Mice Knockout Gastroenterology medicine.disease Molecular biology CCL20 CTGF Real-time polymerase chain reaction Liver Chronic Disease biology.protein RNA |
| Zdroj: | Scandinavian Journal of Gastroenterology. 42:1245-1255 |
| ISSN: | 1502-7708 0036-5521 |
| DOI: | 10.1080/00365520701320521 |
| Popis: | Abcb4 (-/-) mice secrete phosphatidylcholine-free, cytotoxic bile and develop chronic cholangitis. The aim of this study was to identify differentially transcribed genes whose products contribute to the liver tissue pathology during this disease.Hepatic gene transcription was measured in 3-, 6-, 9- and 20-week-old Abcb4 (-/-) mice (FVB.129P2-abcb4(tm1Bor)/J) using cDNA microarrays, with FVB/NJ Abcb4 (+/+) mice serving as controls. Focus was on inflammatory-, remodelling- and fibrosis genes. Marked differential transcription of inflammatory-, tissue remodelling- and fibrosis genes found by cDNA microarrays was verified by real-time polymerase chain reaction (PCR). Liver pathology was quantified by histopathology scoring.Transcription of clade A3 Serpin genes showed early, marked down-regulation. The chemokine genes Ccl2, Ccl20 and Cxcl10 were markedly up-regulated. Tissue remodelling- and fibrosis genes exhibiting markedly up-regulated transcription included: Ctgf, Elf3, Lgals3, Mmp12, Mmp15, Spp1, Loxl2, Pdgfa, Pdgfrb, Sparc, Tgfb1, Tgfb2, Tgfbi, Tgfbr2 and Col1a1, Col1a2, Col2a1, Col3a1, Col4a1 genes. Microarray-based recordings of differential gene transcription of the majority of these genes harmonized with the liver histopathology score. Thus, cDNA microarray-based analysis showed increasing differential transcription of several inflammatory-, tissue remodelling- and fibrosis genes during the first 9 weeks of disease and a tendency towards differential transcription to stabilize at an elevated level from 9 to 20 weeks of disease.Multiple genes regulating inflammation, tissue remodelling and fibrosis not previously linked to Abcb4 (-/-) cholangitis are identified as being differentially transcribed in Abcb4 (-/-) livers, where they contribute to the pathogenesis of liver tissue pathology. |
| Databáze: | OpenAIRE |
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