Zeitschrift für metabolisches Syndrom

Hepatic Gene Expression Associated With Macrophage and Oxidative Stress of Simple Steatosis and Non-Alcoholic Steatohepatitis Model Rats Using DNA Microarray Analysis Microarray Analysis

Abstract

Keiichiro Ohba, Toshio Kumai, Shinichi Iwai, Minoru Watanabe, Go Koizumi,Masayuki Arai, Kanji Furuya, Go Oda, Naoki Matsumoto, Shinichi Kobayashi and Katsuji Oguchi

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.