Hepatic Gene Expression Associated With Macrophage and Oxidative Stress of Simple Steatosis and Non-Alcoholic Steatohepatitis Model Rats Using DNA Microarray Analysis Microarray Analysis
|Keiichiro Ohba1,3*, Toshio Kumai3, Shinichi Iwai1, Minoru Watanabe4, Go Koizumi1,3, Masayuki Arai1, Kanji Furuya1, Go Oda3, Naoki Matsumoto2, Shinichi Kobayashi1 and Katsuji Oguchi1|
|1Department of Pharmacology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan|
|2Department of Pharmacology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa 216-8511, Japan|
|3Department of Pharmacogenomics, St. Marianna University Graduate School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa 216-8511, Japan|
|4Institute for Animal Experimentation, St. Marianna University Graduate School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa 216-8511, Japan|
|Corresponding Author :||Keiichiro Ohba
Department of Pharmacology
Showa University School of Medicine
1-5-8, Hatanodai, Shinagawa-ku
Tokyo 142-8555, Japan
Tel: +81 3 3784 8125
Fax: +81 3 3787 4790
E-mail: [email protected]
|Received October 01, 2012; Accepted November 15, 2012; Published November 17, 2012|
|Citation: Ohba K, Kumai T, Iwai S, Watanabe M, Koizumi G, et al. (2012) Hepatic Gene Expression Associated With Macrophage and Oxidative Stress of Non-Alcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis Model Rats Using DNA Microarray Analysis. J Metabolic Synd 1:115. doi:10.4172/2167-0943.1000115|
|Copyright: © 2012 Ohba K, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.|
Aim: To clarify the mechanism governing progression of Non-Alcoholic Steatohepatitis (NASH), we examined hepatic gene expression associated with macrophage and oxidative stress/inflammation, which plays an important role in the progression of Non-Alcoholic Fatty Liver Disease (NAFLD) in simple steatosis (SS) model and NASH model rats.
Methods: Four-month-old male Spontaneously Hypertensive Hyperlipidemic Rats (SHHR) and Sprague-Dawley (SD) rats were each divided into two groups: SD rats received a high-fat diet and 30% sucrose solution (HFDS) as SS model rats and SHHR received the HFDS as NASH model rats. Microarray analysis was performed on the liver of these rats at eight months of age to select those gene sets, e.g., “genes correlated with progression of NAFLD” and “genes expressed exclusively in NASH”, which are related to macrophage or oxidative stress/inflammation.
Results: Thirteen genes were selected from the microarray analysis data. Four genes were associated with macrophage: acid phosphatase 5, tartrate-resistant (Acp5), a member of the RAS oncogene family (Rab8a), scavenger receptor class B, member 2 (Scarb2) and CD36 molecule (Cd36). Nine genes were associated with oxidative stress/inflammation: translocator protein (Tspo), prostaglandin I2 synthase (Ptgis), tumor necrosis factor receptor superfamily, member 9 (Tnfrsf9), glutathione S-transferase alpha 5 (Gsta5), regucalcin (Rgn), glutathione S-transferase kappa 1 (Gstk1), disabled homolog 2, mitogen-responsive phosphoprotein (Dab2), glutathione S-transferase mu 5 (Gstm5) and flavin-containing monooxygenase 5 (Fmo5). Acp5, Tspo, Ptgis, Tnfrsf, Gsta5 (upregulated) and Rab8a, Rgn, Gstk1 (down-regulated) were included in genes correlated with progression of NAFLD. Scarb2, Cd36, Dab2 Gstm5 (up-regulated) and Fmo5 (down-regulated) were included in genes expressed in only NASH model rats.
Conclusion: We hypothesized that scavenger receptor class B and glutathione S-transferase play an important role in the progression from simple NAFLD to NASH. Our results afford beneficial data regarding therapeutic targets of progression of NAFLD/NASH.