title: Involvement of the TAGE-RAGE system in non-alcoholic steatohepatitis: Novel treatment strategies.
abstract: Non-alcoholic fatty liver disease (NAFLD) is a major cause of liver disease around the world. It includes a spectrum of conditions from simple steatosis to non-alcoholic steatohepatitis (NASH) and can lead to fibrosis, cirrhosis, liver failure, and/or hepatocellular carcinoma. NAFLD is also associated with other medical conditions such as obesity, diabetes mellitus (DM), metabolic syndrome, hypertension, insulin resistance, hyperlipidemia, and cardiovascular disease (CVD). In diabetes, chronic hyperglycemia contributes to the development of both macro- and microvascular conditions through a variety of metabolic pathways. Thus, it can cause a variety of metabolic and hemodynamic conditions, including upregulated advanced glycation end-products (AGEs) synthesis. In our previous study, the most abundant type of toxic AGEs (TAGE); i.e., glyceraldehyde-derived AGEs, were found to make a significant contribution to the pathogenesis of DM-induced angiopathy. Furthermore, accumulating evidence suggests that the binding of TAGE with their receptor (RAGE) induces oxidative damage, promotes inflammation, and causes changes in intracellular signaling and the expression levels of certain genes in various cell populations including hepatocytes and hepatic stellate cells. All of these effects could facilitate the pathogenesis of hypertension, cancer, diabetic vascular complications, CVD, dementia, and NASH. Thus, inhibiting TAGE synthesis, preventing TAGE from binding to RAGE, and downregulating RAGE expression and/or the expression of associated effector molecules all have potential as therapeutic strategies against NASH. Here, we examine the contributions of RAGE and TAGE to various conditions and novel treatments that target them in order to prevent the development and/or progression of NASH.
authors.affiliation: 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.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Takeuchi
authors.affiliation: 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.
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Takino
authors.affiliation: 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.
authors.forename: Akiko
authors.initials: A
authors.lastname: Sakasai-Sakai
authors.affiliation: 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.
authors.forename: Takanobu
authors.initials: T
authors.lastname: Takata
authors.affiliation: 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.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ueda
authors.affiliation: 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.
authors.forename: Mikihiro
authors.initials: M
authors.lastname: Tsutsumi
authors.affiliation: 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.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Hyogo
authors.affiliation: 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.
authors.forename: Sho-Ichi
authors.initials: S
authors.lastname: Yamagishi
keywords: Advanced glycation end-products; Cardiovascular disease; Diabetes mellitus; Dietary advanced glycation end-products; Dietary fructose; Non-alcoholic fatty liver disease; Non-alcoholic steatohepatitis; Receptor for advanced glycation end-products; Toxic advanced glycation end-products; Toxic advanced glycation end-products-receptor for advanced glycation end-products system