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.
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RAGE：FGF1 治疗糖尿病介导的肝损伤期间的潜在治疗靶点
DOI：
10.1111/jcmm.16446
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发表时间：
2021-05
影响因子：
5.3
通讯作者：
Xiao J
中科院分区：
文献类型：
--
作者：
Zheng P;Tang Z;Xiong J;Wang B;Xu J;Chen L;Cai S;Wu C;Ye L;Xu K;Chen Z;Wu Y;Xiao J
糖尿病作为一种严重的代谢性疾病，引起一系列并发症，严重危害人类健康。肝脏是代谢葡萄糖和脂质的关键器官，这在很大程度上有助于胰岛素抵抗和2型糖尿病（T2DM）的发展。外源性成纤维细胞生长因子1（FGF1）在糖尿病的治疗中具有巨大的潜力。晚期糖基化终末产物受体（Receptor of Advanced Glycation End Products，RECEPTOR）是一种参与糖尿病并发症发生的晚期糖基化终末产物受体。先前的研究表明，FGF1可显著改善糖尿病介导的肝损伤（DMLD）。不过，目前尚不清楚这一过程中是否涉及到了马云。在这项研究中，我们腹腔注射0.5毫克/公斤FGF1的db/db小鼠。我们证实，FGF1治疗不仅显著改善了糖尿病诱导的肝脏细胞凋亡，而且还减轻了糖尿病诱导的炎症，从而有助于改善肝功能障碍。此外，我们发现糖尿病触发肝细胞中的β-淀粉样蛋白升高，而FGF1治疗阻断了它，这表明β-淀粉样蛋白可能是FGF1治疗糖尿病诱导的肝损伤的关键靶点。因此，我们进一步证实了在高糖条件下FGF1处理AML 12细胞中，FGF1在AML 12细胞中的作用。我们发现D-核糖，一种β激动剂，逆转了FGF1在AML 12细胞中的保护作用。这些发现表明，FGF1通过抑制TGF β 1通路改善糖尿病诱导的肝细胞凋亡和炎症升高。这些结果表明，DMLD的治疗可能是一个潜在的治疗靶点。
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.
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