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World J Hepatol. Dec 27, 2014; 6(12): 880-893
Published online Dec 27, 2014. doi: 10.4254/wjh.v6.i12.880
Published online Dec 27, 2014. doi: 10.4254/wjh.v6.i12.880
Involvement of the TAGE-RAGE system in non-alcoholic steatohepatitis: Novel treatment strategies
Masayoshi Takeuchi, Akiko Sakasai-Sakai, Takanobu Takata, Tadashi Ueda, Department of Advanced Medicine, Medical Research Institute, Kanazawa Medical University, Uchinada-machi, Ishikawa 920-0293, Japan
Jun-ichi Takino, Laboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Hiroshima International University, Kure, Hiroshima 737-0112, Japan
Mikihiro Tsutsumi, Department of Hepatology, Kanazawa Medical University, Uchinada-machi, Ishikawa 920-0293, Japan
Hideyuki Hyogo, Department of Gastroenterology and Metabolism, Hiroshima University Hospital, Hiroshima 734-8551, Japan
Sho-ichi Yamagishi, Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan
Author contributions: All of the authors contributed to this paper.
Supported by The Japan Society for the Promotion of Science (JSPS) KAKENHI Grant, No. 19300254, 22300264 and 25282029 (Takeuchi M); Kanazawa Medical University, No. SR2012-04 (Tsutsumi M); the Ministry of Education, Culture, Sports, Science, and Technology (MEXT), Regional Innovation Strategy Support Program (Takeuchi M)
Correspondence to: Dr. Masayoshi Takeuchi, Department of Advanced Medicine, Medical Research Institute, Kanazawa Medical University, Uchinada-machi, Ishikawa 920-0293, Japan. takeuchi@kanazawa-med.ac.jp
Telephone: +81-076-2188456 Fax: +81-076-2863652
Received: August 12, 2014
Revised: October 22, 2014
Accepted: October 28, 2014
Published online: December 27, 2014
Processing time: 123 Days and 5.2 Hours
Revised: October 22, 2014
Accepted: October 28, 2014
Published online: December 27, 2014
Processing time: 123 Days and 5.2 Hours
Core Tip
Core tip: Toxic advanced glycation end-products (TAGE) synthesis is increased by non-alcoholic steatohepatitis (NASH), and patients with NASH exhibit significantly increased serum and hepatic TAGE concentrations. Interactions between TAGE and the receptor for advanced glycation end-products (RAGE) have been suggested to cause oxidative stress and increase the fibrogenic potential of cultured human hepatic stellate cells. Therefore, TAGE signaling via RAGE and the resultant synthesis of reactive oxygen species might play a role in the worsening of hepatic pathology seen in NASH. These observations led us to suggest that extracellular and intracellular TAGE are involved in the pathogenesis of NASH.