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  2. RAGE: A potential therapeutic target during FGF1 treatment of diabetes-mediated liver injury

RAGE: A potential therapeutic target during FGF1 treatment of diabetes-mediated liver injury

  • J Cell Mol Med. 2021 May;25(10):4776-4785. doi: 10.1111/jcmm.16446.
Peipei Zheng 1 2 Zonghao Tang 3 Jun Xiong 1 Beini Wang 1 Jingyu Xu 2 Lulu Chen 1 Shufang Cai 2 Chengbiao Wu 4 Libing Ye 1 Ke Xu 2 Zimiao Chen 1 Yanqing Wu 2 Jian Xiao 1
Affiliations

Affiliations

  • 1 Department of Endocrinology, The First Affiliated Hospital and School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China.
  • 2 The Institute of Life Sciences, Wenzhou University, Wenzhou, China.
  • 3 Key Laboratory of Medical Electrophysiology of Ministry of Education, Drug Discovery Research Center, Southwest Medical University, Luzhou, China.
  • 4 Clinical Research Center, Affiliated Xiangshan Hospital, Wenzhou Medical 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.

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