|
|||||
|
|
RAGE: A potential therapeutic target during FGF1 treatment of diabetes-mediated liver injury |
|
| Authors: | Peipei Zheng Zonghao Tang Jun Xiong Beini Wang Jingyu Xu Lulu Chen Shufang Cai Chengbiao Wu Libing Ye Ke Xu Zimiao Chen Yanqing Wu Jian Xiao |
| Affiliation: | 1. Department of Endocrinology, The First Affiliated Hospital and School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China The Institute of Life Sciences, Wenzhou University, Wenzhou, China Contribution: Data curation (equal);2. Key Laboratory of Medical Electrophysiology of Ministry of Education, Drug Discovery Research Center, Southwest Medical University, Luzhou, China Contribution: Data curation (equal);3. Department of Endocrinology, The First Affiliated Hospital and School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China;4. Department of Endocrinology, The First Affiliated Hospital and School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China Contribution: Data curation (supporting);5. The Institute of Life Sciences, Wenzhou University, Wenzhou, China Contribution: Data curation (supporting);6. Clinical Research Center, Affiliated Xiangshan Hospital, Wenzhou Medical University, Wenzhou, China Contribution: Funding acquisition (supporting), Writing - review & editing (supporting);7. Department of Endocrinology, The First Affiliated Hospital and School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China Contribution: Formal analysis (supporting), Writing - review & editing (supporting);8. The Institute of Life Sciences, Wenzhou University, Wenzhou, China |
| Abstract: | As a serious metabolic disease, diabetes causes series of complications that seriously endanger human health. The liver is a key organ for metabolizing glucose and lipids, which substantially contributes to the development of insulin resistance and type 2 diabetes mellitus (T2DM). Exogenous fibroblast growth factor 1 (FGF1) has a great potential for the treatment of diabetes. Receptor of advanced glycation end products (RAGE) is a receptor for advanced glycation end products that involved in the development of diabetes-triggered complications. Previous study has demonstrated that FGF1 significantly ameliorates diabetes-mediated liver damage (DMLD). However, whether RAGE is involved in this process is still unknown. In this study, we intraperitoneally injected db/db mice with 0.5 mg/kg FGF1. We confirmed that FGF1 treatment not only significantly ameliorates diabetes-induced elevated apoptosis in the liver, but also attenuates diabetes-induced inflammation, then contributes to ameliorate liver dysfunction. Moreover, we found that diabetes triggers the elevated RAGE in hepatocytes, and FGF1 treatment blocks it, suggesting that RAGE may be a key target during FGF1 treatment of diabetes-induced liver injury. Thus, we further confirmed the role of RAGE in FGF1 treatment of AML12 cells under high glucose condition. We found that D-ribose, a RAGE agonist, reverses the protective role of FGF1 in AML12 cells. These findings suggest that FGF1 ameliorates diabetes-induced hepatocyte apoptosis and elevated inflammation via suppressing RAGE pathway. These results suggest that RAGE may be a potential therapeutic target for the treatment of DMLD. |
| Keywords: | apoptosis diabetes-mediated liver damage fibroblast growth factor 1 inflammation receptor of advanced glycation end products |