N 6-甲基腺苷去甲基化酶 FTO 控制糖尿病血管病变中巨噬细胞的稳态

IF 6.2 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Diabetes Pub Date : 2024-10-24 DOI:10.2337/db24-0691
Siguo Feng, Qiuyang Zhang, Qing Liu, Chang Huang, Huiying Zhang, Fengsheng Wang, Yue Zhu, Qizhi Jian, Xue Chen, Qin Jiang, Biao Yan
{"title":"N 6-甲基腺苷去甲基化酶 FTO 控制糖尿病血管病变中巨噬细胞的稳态","authors":"Siguo Feng, Qiuyang Zhang, Qing Liu, Chang Huang, Huiying Zhang, Fengsheng Wang, Yue Zhu, Qizhi Jian, Xue Chen, Qin Jiang, Biao Yan","doi":"10.2337/db24-0691","DOIUrl":null,"url":null,"abstract":"Diabetic vasculopathy, encompassing complications such as diabetic retinopathy, represents a significant source of morbidity, with inflammation playing a pivotal role in the progression of these complications. This study investigates the influence of m6A modification and the m6A demethylase FTO on macrophage polarization and its subsequent effects on diabetic microvasculopathy. We found that diabetes induces a shift in macrophage polarization towards a pro-inflammatory M1 phenotype, which is associated with a reduction in m6A modification levels. Notably, FTO emerges as a critical regulator of m6A under diabetic conditions. In vitro experiments reveal that FTO not only modulates macrophage polarization but also mediates their interactions with vascular endothelial cells. In vivo experiments demonstrate that FTO deficiency exacerbates retinal inflammation and microvascular dysfunction in diabetic retinas. Mechanistically, FTO stabilizes mRNA through an m6A-YTHDF2-dependent pathway, thereby activating the PI3K/AKT signaling cascade. Collectively, these findings position FTO as a promising therapeutic target for the management of diabetic vascular complications.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"58 1","pages":""},"PeriodicalIF":6.2000,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"N 6-Methyladenosine demethylase FTO controls macrophage homeostasis in diabetic vasculopathy\",\"authors\":\"Siguo Feng, Qiuyang Zhang, Qing Liu, Chang Huang, Huiying Zhang, Fengsheng Wang, Yue Zhu, Qizhi Jian, Xue Chen, Qin Jiang, Biao Yan\",\"doi\":\"10.2337/db24-0691\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Diabetic vasculopathy, encompassing complications such as diabetic retinopathy, represents a significant source of morbidity, with inflammation playing a pivotal role in the progression of these complications. This study investigates the influence of m6A modification and the m6A demethylase FTO on macrophage polarization and its subsequent effects on diabetic microvasculopathy. We found that diabetes induces a shift in macrophage polarization towards a pro-inflammatory M1 phenotype, which is associated with a reduction in m6A modification levels. Notably, FTO emerges as a critical regulator of m6A under diabetic conditions. In vitro experiments reveal that FTO not only modulates macrophage polarization but also mediates their interactions with vascular endothelial cells. In vivo experiments demonstrate that FTO deficiency exacerbates retinal inflammation and microvascular dysfunction in diabetic retinas. Mechanistically, FTO stabilizes mRNA through an m6A-YTHDF2-dependent pathway, thereby activating the PI3K/AKT signaling cascade. Collectively, these findings position FTO as a promising therapeutic target for the management of diabetic vascular complications.\",\"PeriodicalId\":11376,\"journal\":{\"name\":\"Diabetes\",\"volume\":\"58 1\",\"pages\":\"\"},\"PeriodicalIF\":6.2000,\"publicationDate\":\"2024-10-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Diabetes\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2337/db24-0691\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Diabetes","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2337/db24-0691","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0

摘要

糖尿病血管病变包括糖尿病视网膜病变等并发症,是发病率的重要来源,而炎症在这些并发症的发展过程中起着关键作用。本研究探讨了 m6A 修饰和 m6A 去甲基化酶 FTO 对巨噬细胞极化的影响及其随后对糖尿病微血管病变的影响。我们发现,糖尿病诱导巨噬细胞极化转向促炎的 M1 表型,这与 m6A 修饰水平的降低有关。值得注意的是,FTO 是糖尿病条件下 m6A 的关键调节因子。体外实验显示,FTO 不仅能调节巨噬细胞的极化,还能介导它们与血管内皮细胞的相互作用。体内实验证明,FTO 缺乏会加剧糖尿病视网膜炎症和微血管功能障碍。从机制上讲,FTO 通过依赖 m6A-YTHDF2 的途径稳定 mRNA,从而激活 PI3K/AKT 信号级联。总之,这些发现将 FTO 定位为治疗糖尿病血管并发症的一个有前景的治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
N 6-Methyladenosine demethylase FTO controls macrophage homeostasis in diabetic vasculopathy
Diabetic vasculopathy, encompassing complications such as diabetic retinopathy, represents a significant source of morbidity, with inflammation playing a pivotal role in the progression of these complications. This study investigates the influence of m6A modification and the m6A demethylase FTO on macrophage polarization and its subsequent effects on diabetic microvasculopathy. We found that diabetes induces a shift in macrophage polarization towards a pro-inflammatory M1 phenotype, which is associated with a reduction in m6A modification levels. Notably, FTO emerges as a critical regulator of m6A under diabetic conditions. In vitro experiments reveal that FTO not only modulates macrophage polarization but also mediates their interactions with vascular endothelial cells. In vivo experiments demonstrate that FTO deficiency exacerbates retinal inflammation and microvascular dysfunction in diabetic retinas. Mechanistically, FTO stabilizes mRNA through an m6A-YTHDF2-dependent pathway, thereby activating the PI3K/AKT signaling cascade. Collectively, these findings position FTO as a promising therapeutic target for the management of diabetic vascular complications.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Diabetes
Diabetes 医学-内分泌学与代谢
CiteScore
12.50
自引率
2.60%
发文量
1968
审稿时长
1 months
期刊介绍: Diabetes is a scientific journal that publishes original research exploring the physiological and pathophysiological aspects of diabetes mellitus. We encourage submissions of manuscripts pertaining to laboratory, animal, or human research, covering a wide range of topics. Our primary focus is on investigative reports investigating various aspects such as the development and progression of diabetes, along with its associated complications. We also welcome studies delving into normal and pathological pancreatic islet function and intermediary metabolism, as well as exploring the mechanisms of drug and hormone action from a pharmacological perspective. Additionally, we encourage submissions that delve into the biochemical and molecular aspects of both normal and abnormal biological processes. However, it is important to note that we do not publish studies relating to diabetes education or the application of accepted therapeutic and diagnostic approaches to patients with diabetes mellitus. Our aim is to provide a platform for research that contributes to advancing our understanding of the underlying mechanisms and processes of diabetes.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信