Involvement of the TAGE-RAGE system in non-alcoholic steatohepatitis: Novel treatment strategies

作     者：Masayoshi Takeuchi Jun-ichi Takino Akiko Sakasai-Sakai Takanobu Takata Tadashi Ueda Mikihiro Tsutsumi Hideyuki Hyogo Sho-ichi Yamagishi 

作者机构：Department of Advanced Medicine Medical Research Institute Kanazawa Medical University Uchinadamachi Ishikawa 920-0293 Japan Laboratory of Biochemistry Faculty of Pharmaceutical Sciences Hiroshima International University Kure Hiroshima 737-0112 Japan Department of Hepatology Kanazawa Medical University Uchinada-machi Ishikawa 920-0293 Japan Department of Gastroenterology and Metabolism Hiroshima University Hospital Hiroshima 734-8551 Japan Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications Kurume University School of Medicine Kurume Fukuoka 830-0011 Japan 

出 版 物：《World Journal of Hepatology》 (世界肝病学杂志（英文版）（电子版）)

年 卷 期：2014年第6卷第12期

页      面：880-893页

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：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) 

主　　题：Non-alcoholic fatty liver disease Non-alcoholic steatohepatitis Advanced glycation end-products Toxic advanced glycation end-products Receptor for advanced glycation end-products Toxic advanced glycation end-products-receptor for advanced glycation end-products system Diabetes mellitus Cardiovascular disease Dietary fructose Dietary advanced glycation end-products 

摘      要：Non-alcoholic fatty liver disease(NAFLD)is a major cause of liver disease around the *** includes a spectrum of conditions from simple steatosis to non-alcoholic steatohepatitis(NASH)and can lead to fibrosis,cirrhosis,liver failure,and/or hepatocellular *** is also associated with other medical conditions such as obesity,diabetes mellitus(DM),metabolic syn-drome,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 ***,it can cause a variety of metabolic and hemodynamic conditions,including upregulated advanced glycation end-products(AGEs)*** 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 ***,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 *** of these effects could facilitate the pathogenesis of hypertension,cancer,diabetic vascular complications,CVD,dementia,and ***,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 ***,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.