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

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.

• 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
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 25 Issue 10 Pg. 4776-4785 (05 2021) ISSN: 1582-4934 [Electronic] England
• PMID: 33788387 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

Chemical References

• Ager protein, mouse
• Receptor for Advanced Glycation End Products
• Fibroblast Growth Factor 1

Topics

• Acute Lung Injury (drug therapy, etiology, metabolism, pathology)
• Animals
• Apoptosis
• Diabetes Complications (drug therapy, etiology, metabolism, pathology)
• Diabetes Mellitus, Experimental (complications)
• Diabetes Mellitus, Type 2 (complications)
• Fibroblast Growth Factor 1 (pharmacology)
• Inflammation (drug therapy, etiology, metabolism, pathology)
• Male
• Mice
• Mice, Inbred C57BL
• Receptor for Advanced Glycation End Products (antagonists & inhibitors)