{"title":"通过组蛋白乳酰化增强巩膜糖酵解促进近视的形成","authors":"Xiaolei Lin, Yi Lei, Miaozhen Pan, Changxi Hu, Bintao Xie, Wenjing Wu, Jianzhong Su, Yating Li, Yuhan Tan, Xiaohuan Wei, Zhengbo Xue, Ruiyan Xu, Mengqi Di, Hanyu Deng, Shengcong Liu, Xingxing Yang, Jia Qu, Wei Chen, Xiangtian Zhou, Fei Zhao","doi":"10.1016/j.cmet.2023.12.023","DOIUrl":null,"url":null,"abstract":"<p><span>Myopia is characterized of maladaptive increases in scleral fibroblast-to-myofibroblast transdifferentiation<span> (FMT). Scleral hypoxia<span><span> is a significant factor contributing to myopia, but how hypoxia induces myopia is poorly understood. Here, we showed that myopia in mice and guinea pigs was associated with hypoxia-induced increases in key glycolytic enzymes expression and lactate levels in the </span>sclera. Promotion of scleral glycolysis or lactate production induced FMT and myopia; conversely, suppression of glycolysis or lactate production eliminated or inhibited FMT and myopia. Mechanistically, increasing scleral glycolysis-lactate levels promoted FMT and myopia via H3K18la, and this promoted </span></span></span><em>Notch1</em><span> expression. Genetic<span> analyses identified a significant enrichment of two genes encoding glycolytic enzymes, </span></span><span><em>ENO2</em></span> and <span><em>TPI1</em></span><span>. Moreover, increasing sugar intake<span> in guinea pigs not only induced myopia but also enhanced the response to myopia induction via the scleral glycolysis-lactate-histone lactylation pathway. Collectively, we suggest that scleral glycolysis contributes to myopia by promoting FMT via lactate-induced histone lactylation.</span></span></p>","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":null,"pages":null},"PeriodicalIF":27.7000,"publicationDate":"2024-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Augmentation of scleral glycolysis promotes myopia through histone lactylation\",\"authors\":\"Xiaolei Lin, Yi Lei, Miaozhen Pan, Changxi Hu, Bintao Xie, Wenjing Wu, Jianzhong Su, Yating Li, Yuhan Tan, Xiaohuan Wei, Zhengbo Xue, Ruiyan Xu, Mengqi Di, Hanyu Deng, Shengcong Liu, Xingxing Yang, Jia Qu, Wei Chen, Xiangtian Zhou, Fei Zhao\",\"doi\":\"10.1016/j.cmet.2023.12.023\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><span>Myopia is characterized of maladaptive increases in scleral fibroblast-to-myofibroblast transdifferentiation<span> (FMT). Scleral hypoxia<span><span> is a significant factor contributing to myopia, but how hypoxia induces myopia is poorly understood. Here, we showed that myopia in mice and guinea pigs was associated with hypoxia-induced increases in key glycolytic enzymes expression and lactate levels in the </span>sclera. Promotion of scleral glycolysis or lactate production induced FMT and myopia; conversely, suppression of glycolysis or lactate production eliminated or inhibited FMT and myopia. Mechanistically, increasing scleral glycolysis-lactate levels promoted FMT and myopia via H3K18la, and this promoted </span></span></span><em>Notch1</em><span> expression. Genetic<span> analyses identified a significant enrichment of two genes encoding glycolytic enzymes, </span></span><span><em>ENO2</em></span> and <span><em>TPI1</em></span><span>. Moreover, increasing sugar intake<span> in guinea pigs not only induced myopia but also enhanced the response to myopia induction via the scleral glycolysis-lactate-histone lactylation pathway. Collectively, we suggest that scleral glycolysis contributes to myopia by promoting FMT via lactate-induced histone lactylation.</span></span></p>\",\"PeriodicalId\":9840,\"journal\":{\"name\":\"Cell metabolism\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":27.7000,\"publicationDate\":\"2024-01-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell metabolism\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1016/j.cmet.2023.12.023\",\"RegionNum\":1,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell metabolism","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.cmet.2023.12.023","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
Augmentation of scleral glycolysis promotes myopia through histone lactylation
Myopia is characterized of maladaptive increases in scleral fibroblast-to-myofibroblast transdifferentiation (FMT). Scleral hypoxia is a significant factor contributing to myopia, but how hypoxia induces myopia is poorly understood. Here, we showed that myopia in mice and guinea pigs was associated with hypoxia-induced increases in key glycolytic enzymes expression and lactate levels in the sclera. Promotion of scleral glycolysis or lactate production induced FMT and myopia; conversely, suppression of glycolysis or lactate production eliminated or inhibited FMT and myopia. Mechanistically, increasing scleral glycolysis-lactate levels promoted FMT and myopia via H3K18la, and this promoted Notch1 expression. Genetic analyses identified a significant enrichment of two genes encoding glycolytic enzymes, ENO2 and TPI1. Moreover, increasing sugar intake in guinea pigs not only induced myopia but also enhanced the response to myopia induction via the scleral glycolysis-lactate-histone lactylation pathway. Collectively, we suggest that scleral glycolysis contributes to myopia by promoting FMT via lactate-induced histone lactylation.
期刊介绍:
Cell Metabolism is a top research journal established in 2005 that focuses on publishing original and impactful papers in the field of metabolic research.It covers a wide range of topics including diabetes, obesity, cardiovascular biology, aging and stress responses, circadian biology, and many others.
Cell Metabolism aims to contribute to the advancement of metabolic research by providing a platform for the publication and dissemination of high-quality research and thought-provoking articles.