The FLS (fatty liver Shionogi) mouse reveals local expressions of lipocalin-2, CXCL1 and CXCL9 in the liver with non-alcoholic steatohepatitis
| Autor: | Osamu Yokosuka, Satomi Nishimura, Kazuyuki Matsushita, Ken Nonaka, Toshihisa Semba, Sayaka Ohno, Fumio Nomura, Fumio Imazeki, Osamu Ohara, Motoi Nishimura, Mamoru Satoh, Kazuyuki Sogawa, Setsu Sawai, Takayuki Ishige |
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| Rok vydání: | 2013 |
| Předmět: |
Pathology
medicine.medical_specialty Cirrhosis Chemokine CXCL1 Pathogenesis Lipocalin Chemokine CXCL9 Statistics Nonparametric Mice Lipocalin-2 Non-alcoholic Fatty Liver Disease Adipokine Nonalcoholic fatty liver disease medicine Animals Non-alcoholic steatohepatitis Oligonucleotide Array Sequence Analysis Oncogene Proteins business.industry Gene Expression Profiling Fatty liver Gastroenterology General Medicine medicine.disease Immunohistochemistry digestive system diseases Lipocalins Up-Regulation Reverse transcription polymerase chain reaction Gene expression profiling Fatty Liver Disease Models Animal Liver Chemokine Hepatocellular carcinoma Cancer research Hepatocytes Steatohepatitis business Transcriptome Acute-Phase Proteins Research Article |
| Zdroj: | BMC Gastroenterology |
| ISSN: | 1471-230X |
| Popis: | Background Nonalcoholic fatty liver disease (NAFLD) encompasses a wide spectrum of diseases, ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), which carries a significant risk of progression to cirrhosis and hepatocellular carcinoma. Since NASH is a progressive but reversible condition, it is desirable to distinguish NASH from simple steatosis, and to treat NASH patients at an early stage. To establish appropriate diagnosis and therapy, the pathological mechanisms of the disease should be elucidated; however, these have not been fully clarified for both NASH and simple steatosis. This study aims to reveal the differences between simple steatosis and NASH. Methods This study used fatty liver Shionogi (FLS) mice as a NASH model, for comparison with dd Shionogi (DS) mice as a model of simple steatosis. Genome-wide gene expression analysis was performed using Affymetrix GeneChip Mouse Genome 430 2.0 Array, which contains 45101 probe sets for known and predicted genes. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry were used to investigate gene expression changes and protein localizations. Results DNA microarray analysis of the liver transcriptomes and qRT-PCR of both types of mice revealed that LCN2, CXCL1 and CXCL9 mRNAs were overexpressed in FLS mouse livers. Immunohistochemistry showed that CXCL1 protein was mainly localized to steatotic hepatocytes. CXCL9 protein-expressing hepatocytes and sinusoidal endothelium were localized in some areas of inflammatory cell infiltration. Most interestingly, hepatocytes expressing LCN2, a kind of adipokine, were localized around almost all inflammatory cell clusters. Furthermore, there was a positive correlation between the number of LCN2-positive hepatocytes in the specimen and the number of inflammatory foci. Conclusions Overexpression and distinct localization of LCN2, CXCL1 and CXCL9 in the liver of fatty liver Shionogi mice suggest significant roles of these proteins in the pathogenesis of NASH. |
| Databáze: | OpenAIRE |
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