文献检索文档翻译深度研究
Suppr Zotero 插件Zotero 插件
邀请有礼套餐&价格历史记录

新学期，新优惠

限时优惠:9月1日-9月22日

30天高级会员仅需29元

1天体验卡首发特惠仅需5.99元

了解详情
不再提醒
插件&应用
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
高级版
套餐订阅购买积分包
AI 工具
文献检索文档翻译深度研究
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2025

METTL3 介导的 HMGA2 mRNA m6A 修饰促进视网膜下纤维化和上皮-间充质转化。

METTL3-mediated m6A modification of HMGA2 mRNA promotes subretinal fibrosis and epithelial-mesenchymal transition.

机构信息

Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.

Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai 200080, China.

出版信息

J Mol Cell Biol. 2023 Aug 3;15(3). doi: 10.1093/jmcb/mjad005.

DOI:10.1093/jmcb/mjad005
PMID:36945110
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10603769/
Abstract

Subretinal fibrosis is a major cause of the poor visual prognosis for patients with neovascular age-related macular degeneration (nAMD). Myofibroblasts originated from retinal pigment epithelial (RPE) cells through epithelial-mesenchymal transition (EMT) contribute to the fibrosis formation. N6-Methyladenosine (m6A) modification has been implicated in the EMT process and multiple fibrotic diseases. The role of m6A modification in EMT-related subretinal fibrosis has not yet been elucidated. In this study, we found that during subretinal fibrosis in the mouse model of laser-induced choroidal neovascularization, METTL3 was upregulated in RPE cells. Through m6A epitranscriptomic microarray and further verification, high-mobility group AT-hook 2 (HMGA2) was identified as the key downstream target of METTL3, subsequently activating potent EMT-inducing transcription factor SNAIL. Finally, by subretinal injections of adeno-associated virus vectors, we confirmed that METTL3 deficiency in RPE cells could efficiently attenuate subretinal fibrosis in vivo. In conclusion, our present research identified an epigenetic mechanism of METTL3-m6A-HMGA2 in subretinal fibrosis and EMT of RPE cells, providing a novel therapeutic target for subretinal fibrosis secondary to nAMD.

摘要

视网膜下纤维化是新生血管性年龄相关性黄斑变性（nAMD）患者视力预后不良的主要原因。成纤维细胞来源于视网膜色素上皮（RPE）细胞，通过上皮-间充质转化（EMT）形成纤维化。N6-甲基腺苷（m6A）修饰参与 EMT 过程和多种纤维化疾病。m6A 修饰在 EMT 相关的视网膜下纤维化中的作用尚未阐明。在这项研究中，我们发现，在激光诱导脉络膜新生血管化的小鼠模型中，视网膜下纤维化时，RPE 细胞中的 METTL3 上调。通过 m6A 转录组学微阵列和进一步验证，发现高迁移率族 AT 盒 2（HMGA2）是 METTL3 的关键下游靶标，随后激活强效 EMT 诱导转录因子 SNAIL。最后，通过 RPE 细胞的腺相关病毒载体的视网膜下注射，我们证实 RPE 细胞中 METTL3 的缺失可以有效地减轻体内的视网膜下纤维化。总之，本研究确定了 METTL3-m6A-HMGA2 在视网膜下纤维化和 RPE 细胞 EMT 中的表观遗传机制，为 nAMD 引起的视网膜下纤维化提供了新的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26d7/10603769/029003ebee39/mjad005fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26d7/10603769/8a67ef9df7e2/mjad005fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26d7/10603769/59928c2bd173/mjad005fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26d7/10603769/25b2d5f5fa31/mjad005fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26d7/10603769/b917a61d0c6e/mjad005fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26d7/10603769/6aa8c18ecc87/mjad005fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26d7/10603769/54d9a953d0fb/mjad005fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26d7/10603769/029003ebee39/mjad005fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26d7/10603769/8a67ef9df7e2/mjad005fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26d7/10603769/59928c2bd173/mjad005fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26d7/10603769/25b2d5f5fa31/mjad005fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26d7/10603769/b917a61d0c6e/mjad005fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26d7/10603769/6aa8c18ecc87/mjad005fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26d7/10603769/54d9a953d0fb/mjad005fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26d7/10603769/029003ebee39/mjad005fig7.jpg

相似文献

[1]
METTL3-mediated m6A modification of HMGA2 mRNA promotes subretinal fibrosis and epithelial-mesenchymal transition.

J Mol Cell Biol. 2023-8-3

[2]
METTL3-mediated N6-methyladenosine modification is critical for epithelial-mesenchymal transition and metastasis of gastric cancer.

Mol Cancer. 2019-10-13

[3]
Wnt5a/β-catenin-mediated epithelial-mesenchymal transition: a key driver of subretinal fibrosis in neovascular age-related macular degeneration.

J Neuroinflammation. 2024-3-26

[4]
Complement activation contributes to subretinal fibrosis through the induction of epithelial-to-mesenchymal transition (EMT) in retinal pigment epithelial cells.

J Neuroinflammation. 2022-7-14

[5]
The m6A methyltransferase METTL3 controls epithelial-mesenchymal transition, migration and invasion of breast cancer through the MALAT1/miR-26b/HMGA2 axis.

Cancer Cell Int. 2021-8-21

[6]
METTL3 Mediates Epithelial-Mesenchymal Transition by Modulating FOXO1 mRNA N -Methyladenosine-Dependent YTHDF2 Binding: A Novel Mechanism of Radiation-Induced Lung Injury.

Adv Sci (Weinh). 2023-6

[7]
TGF-β2-induced alterations of m6A methylation in hTERT RPE-1 cells.

Exp Eye Res. 2024-4

[8]
METTL3 attenuates proliferative vitreoretinopathy and epithelial-mesenchymal transition of retinal pigment epithelial cells via wnt/β-catenin pathway.

J Cell Mol Med. 2021-5

[9]
The m6A methyltransferase METTL3 contributes to Transforming Growth Factor-beta-induced epithelial-mesenchymal transition of lung cancer cells through the regulation of JUNB.

Biochem Biophys Res Commun. 2020-1-22

[10]
Human umbilical cord mesenchymal stem cell-derived exosomal miR-27b attenuates subretinal fibrosis via suppressing epithelial-mesenchymal transition by targeting HOXC6.

Stem Cell Res Ther. 2021-1-7

引用本文的文献

[1]
Integration of multi-omics data reveals dysregulated RNA methylation in retinal pigment epithelium drives age-related macular degeneration.

Int J Ophthalmol. 2025-9-18

[2]
METTL3 blocked the progression of diabetic retinopathy through m6A-modified SOX2.

Open Med (Wars). 2025-7-25

[3]
Intracellular Signaling Pathways and Their Potential Targeting for Treatment of Ocular Posterior Segment Fibrosis.

J Ophthalmic Vis Res. 2025-5-21

[4]
Molecular Mechanisms of Epithelial-Mesenchymal Transition in Retinal Pigment Epithelial Cells: Implications for Age-Related Macular Degeneration (AMD) Progression.

Biomolecules. 2025-5-27

[5]
Inhibition of HPSE/SDC-2 axis-induced epithelial-mesenchymal transition for treating IC/BPS.

PLoS One. 2025-5-23

[6]
WTAP-mediated N6-methyladenosine mRNA methylation regulates laser-induced macular neovascularization.

Mol Vis. 2024-10-8

[7]
m6A RNA modification pathway: orchestrating fibrotic mechanisms across multiple organs.

Brief Funct Genomics. 2025-1-15

[8]
Silencing METTL3 Increases HSP70 Expression and Alleviates Fibrosis in Keratocytes.

Invest Ophthalmol Vis Sci. 2024-11-4

[9]
METTL3-mediated m6A modification of SIRT1 mRNA affects the progression of diabetic cataracts through cellular autophagy and senescence.

J Transl Med. 2024-9-27

[10]
N6-methyladenosine (m6A) RNA modification in fibrosis and collagen-related diseases.

Clin Epigenetics. 2024-9-12

本文引用的文献

[1]
m6A modification of circHPS5 and hepatocellular carcinoma progression through HMGA2 expression.

Mol Ther Nucleic Acids. 2021-9-14

[2]
The m6A methyltransferase METTL3 controls epithelial-mesenchymal transition, migration and invasion of breast cancer through the MALAT1/miR-26b/HMGA2 axis.

Cancer Cell Int. 2021-8-21

[3]
Transcriptome Landscape of Epithelial to Mesenchymal Transition of Human Stem Cell-Derived RPE.

Invest Ophthalmol Vis Sci. 2021-4-1

[4]
METTL3 attenuates proliferative vitreoretinopathy and epithelial-mesenchymal transition of retinal pigment epithelial cells via wnt/β-catenin pathway.

J Cell Mol Med. 2021-5

[5]
Genistein Ameliorates Renal Fibrosis Through Regulation Snail via m6A RNA Demethylase ALKBH5.

Front Pharmacol. 2020-11-19

[6]
Macrophage to myofibroblast transition contributes to subretinal fibrosis secondary to neovascular age-related macular degeneration.

J Neuroinflammation. 2020-11-25

[7]
HMGA2-induced epithelial-mesenchymal transition is reversed by let-7d in intrauterine adhesions.

Mol Hum Reprod. 2021-2-5

[8]
Silencing of METTL3 attenuates cardiac fibrosis induced by myocardial infarction via inhibiting the activation of cardiac fibroblasts.

FASEB J. 2021-2

[9]
Emerging roles for HMGA2 in colorectal cancer.

Transl Oncol. 2021-1

[10]
ROS production and mitochondrial dysfunction driven by PU.1-regulated NOX4-p22 activation in Aβ-induced retinal pigment epithelial cell injury.

Theranostics. 2020

文献AI研究员

20分钟写一篇综述，助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

推荐工具

医学文档翻译智能文献检索