The FLS (Fatty liver Shionogi) mouse reveals local expressions of lipocalin-2, CXCL1 and CXCL9 in the liver with non-alcoholic steatohepatitis

BMC Gastroenterology

Fumio Nomura²  Osamu Yokosuka⁴  Fumio Imazeki⁴  Kazuyuki Matsushita²  Setsu Sawai²  Mamoru Satoh²  Kazuyuki Sogawa²  Ken Nonaka⁵  Sayaka Ohno¹  Takayuki Ishige³  Osamu Ohara⁵  Satomi Nishimura³  Motoi Nishimura²  Toshihisa Semba³ 

[1]Division of Laboratory Medicine, Chiba University Hospital, 2-6-7 Kazusa-kamatari, Kisarazu, Chiba 292-0818, Japan

[2]Clinical Proteomics Research Center, Chiba University Hospital, Chiba, Japan

[3]Department of Molecular Diagnosis, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan

[4]Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan

[5]Department of Human Genome Research, Kazusa DNA Research Institute, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan

关键词: Pathogenesis;    Immunohistochemistry;    Chemokine;    Non-alcoholic steatohepatitis;    Adipokine;   

Others  :  857757
DOI  :  10.1186/1471-230X-13-120

 received in 2013-03-21, accepted in 2013-07-09,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Semba et al.; licensee BioMed Central Ltd.

【 图 表 】

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