• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
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
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
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 @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

FOXO1和FOXO4转录因子与晶状体发育的联系。

The link of FOXO1 and FOXO4 transcription factors to development of the lens.

作者信息

Gheyas Rifah N, Williams Ruby C, Ryan Kelly A, Menko A Sue

机构信息

Department of Pathology and Genomic Medicine, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.

Department of Ophthalmology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.

出版信息

Dev Dyn. 2025 Jan 11. doi: 10.1002/dvdy.766.

DOI:10.1002/dvdy.766
PMID:39797725
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12246175/
Abstract

BACKGROUND

The FOXOs regulate the transcription of many genes, including ones directly linked to pathways required for lens development. However, this transcription factor family has rarely been studied in the context of development, including the development of the lens. FOXO expression, regulation, and function during lens development remained unexplored.

RESULTS

In studies of the embryonic lens, we showed that both FOXO1 and FOXO4, which share many downstream targets, are expressed in a differentiation-state-specific manner, most highly in lens epithelial and differentiating cortical fiber cells. Their expression patterns and subcellular distributions suggest both shared and distinct functions. Stabilization of FOXO cytoplasmic pools involved their binding to the chaperone protein 14-3-3. FOXO association with β-catenin linked this transcription complex to fiber cell-specific gene activation. Inhibition of PI3K/Akt signaling promoted FOXO1/FOXO4 nuclear localization in lens epithelial and fiber cells and expression of the CDKi p27 in the lens epithelium where it has been linked to lens cell withdrawal from the cell cycle and initiation of the lens differentiation program. We showed that FOXO1 transcriptional activation is required for the induction of p27 when Akt signaling is blocked, demonstrating the linearity of the PI3K/Akt/FOXO1/p27 pathway.

CONCLUSIONS

PI3K/Akt signaling regulates FOXO-dependent lens cell differentiation.

摘要

背景

FOXO转录因子可调控许多基因的转录，包括与晶状体发育所需信号通路直接相关的基因。然而，在包括晶状体发育在内的发育过程中，对这个转录因子家族的研究甚少。晶状体发育过程中FOXO的表达、调控及功能仍未得到探索。

结果

在胚胎晶状体研究中，我们发现具有许多共同下游靶点的FOXO1和FOXO4均以分化状态特异性方式表达，在晶状体上皮细胞和分化中的皮质纤维细胞中表达最高。它们的表达模式和亚细胞分布提示了其功能既有共同之处，也有不同之处。FOXO在细胞质中的稳定存在涉及其与伴侣蛋白14-3-3的结合。FOXO与β-连环蛋白的结合将这个转录复合体与纤维细胞特异性基因激活联系起来。抑制PI3K/Akt信号通路可促进FOXO1/FOXO4在晶状体上皮细胞和纤维细胞中的核定位，并促进晶状体上皮细胞中细胞周期蛋白依赖性激酶抑制因子p27的表达，p27与晶状体细胞退出细胞周期及启动晶状体分化程序有关。我们发现，当Akt信号通路被阻断时，诱导p27表达需要FOXO1的转录激活，这证明了PI3K/Akt/FOXO1/p27信号通路的线性关系。

结论

PI3K/Akt信号通路调控FOXO依赖的晶状体细胞分化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d39f/12271660/1e4fb1bd5ec2/DVDY-254-829-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d39f/12271660/17039a64f034/DVDY-254-829-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d39f/12271660/f1452fa19d27/DVDY-254-829-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d39f/12271660/fcce2859b2f7/DVDY-254-829-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d39f/12271660/628947dc388a/DVDY-254-829-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d39f/12271660/446eb4be27b5/DVDY-254-829-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d39f/12271660/7a05cd6ad62f/DVDY-254-829-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d39f/12271660/13164b116ad1/DVDY-254-829-g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d39f/12271660/76089833410b/DVDY-254-829-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d39f/12271660/83a334c9067e/DVDY-254-829-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d39f/12271660/f77b3c9c3802/DVDY-254-829-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d39f/12271660/83fe0341ecb2/DVDY-254-829-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d39f/12271660/7052a341d379/DVDY-254-829-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d39f/12271660/1e4fb1bd5ec2/DVDY-254-829-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d39f/12271660/17039a64f034/DVDY-254-829-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d39f/12271660/f1452fa19d27/DVDY-254-829-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d39f/12271660/fcce2859b2f7/DVDY-254-829-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d39f/12271660/628947dc388a/DVDY-254-829-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d39f/12271660/446eb4be27b5/DVDY-254-829-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d39f/12271660/7a05cd6ad62f/DVDY-254-829-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d39f/12271660/13164b116ad1/DVDY-254-829-g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d39f/12271660/76089833410b/DVDY-254-829-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d39f/12271660/83a334c9067e/DVDY-254-829-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d39f/12271660/f77b3c9c3802/DVDY-254-829-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d39f/12271660/83fe0341ecb2/DVDY-254-829-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d39f/12271660/7052a341d379/DVDY-254-829-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d39f/12271660/1e4fb1bd5ec2/DVDY-254-829-g003.jpg

相似文献

1
The link of FOXO1 and FOXO4 transcription factors to development of the lens.FOXO1和FOXO4转录因子与晶状体发育的联系。
Dev Dyn. 2025 Jan 11. doi: 10.1002/dvdy.766.
2
Overexpression of HepaCAM inhibits bladder cancer cell proliferation and viability through the AKT/FoxO pathway.HepaCAM的过表达通过AKT/FoxO信号通路抑制膀胱癌细胞的增殖和活力。
J Cancer Res Clin Oncol. 2017 May;143(5):793-805. doi: 10.1007/s00432-016-2333-y. Epub 2017 Feb 22.
3
miR-410 Regulates Helper T Cell Differentiation in Ovalbumin-Induced Asthma through the PI3K-AKT-VEGF Signaling Pathway.miR-410 通过 PI3K-AKT-VEGF 信号通路调节卵清蛋白诱导的哮喘中的辅助性 T 细胞分化。
Int Arch Allergy Immunol. 2024;185(1):1-9. doi: 10.1159/000531493. Epub 2023 Sep 19.
4
Mettl3 Regulates Lens Development by Promoting the Differentiation Processes of Secondary Fiber Cells.Mettl3通过促进次级纤维细胞的分化过程来调节晶状体发育。
Invest Ophthalmol Vis Sci. 2025 Jul 1;66(9):45. doi: 10.1167/iovs.66.9.45.
5
Short-Term Memory Impairment短期记忆障碍
6
FOXO-regulated DEAF1 controls muscle regeneration through autophagy.FOXO 调控的 DEAF1 通过自噬控制肌肉再生。
Autophagy. 2024 Dec;20(12):2632-2654. doi: 10.1080/15548627.2024.2374693. Epub 2024 Jul 20.
7
TSC/mTORC1 mediates mTORC2/AKT1 signaling in c-MYC-induced murine hepatocarcinogenesis via centromere protein M.TSC/mTORC1 通过着丝粒蛋白 M 介导 c-MYC 诱导的小鼠肝癌发生中的 mTORC2/AKT1 信号通路。
J Clin Invest. 2024 Sep 26;134(22):e174415. doi: 10.1172/JCI174415.
8
Zinc finger protein 695 facilitates the proliferation of colorectal cancer cells through activation of the NEK2 and PI3K/Akt/mTOR signaling pathways.锌指蛋白695通过激活NEK2和PI3K/Akt/mTOR信号通路促进结肠癌细胞的增殖。
Oncol Rep. 2025 Oct;54(4). doi: 10.3892/or.2025.8949. Epub 2025 Jul 19.
9
Nck1 regulates the in vitro development of human regulatory T cells through AKT pathway.Nck1通过AKT信号通路调控人调节性T细胞的体外发育。
Clin Exp Immunol. 2025 Jan 21;219(1). doi: 10.1093/cei/uxaf011.
10
Foxo1 is required in mouse spermatogonial stem cells for their maintenance and the initiation of spermatogenesis.Foxo1 在小鼠精原干细胞中对于其维持和精子发生的起始是必需的。
J Clin Invest. 2011 Sep;121(9):3456-66. doi: 10.1172/JCI57984. Epub 2011 Aug 25.

本文引用的文献

1
Whole Mount Imaging to Visualize and Quantify Peripheral Lens Structure, Cell Morphology, and Organization.整装成像以可视化和量化晶状体周边结构、细胞形态及组织结构。
J Vis Exp. 2024 Jan 19(203). doi: 10.3791/66017.
2
The link between inhibition of PI3K signaling, induction of autophagy, and elimination of organelles to form the lens organelle-free zone.PI3K信号通路抑制、自噬诱导与细胞器清除之间的联系，以形成晶状体无细胞器区。
Autophagy Rep. 2022;1(1):238-241. doi: 10.1080/27694127.2022.2080315. Epub 2022 May 30.
3
The involvement of caspases in the process of nuclear removal during lens fiber cell differentiation.
半胱天冬酶在晶状体纤维细胞分化过程中细胞核去除过程中的作用。
Cell Death Discov. 2023 Oct 21;9(1):386. doi: 10.1038/s41420-023-01680-y.
4
Multiomic analysis implicates FOXO4 in genetic regulation of chick lens fiber cell differentiation.多组学分析提示 FOXO4 参与了鸡晶状体纤维细胞分化的遗传调控。
Dev Biol. 2023 Dec;504:25-37. doi: 10.1016/j.ydbio.2023.09.005. Epub 2023 Sep 16.
5
Examining PI3K-signaling-dependent regulation of lens organelle free zone formation via immunolocalization and immunoblotting in chick embryos.通过免疫定位和免疫印迹技术在鸡胚中检测 PI3K 信号依赖性调节晶状体细胞器游离区的形成。
STAR Protoc. 2023 Dec 15;4(4):102569. doi: 10.1016/j.xpro.2023.102569. Epub 2023 Sep 14.
6
The expression of p27 in the adult vestibular sensory organs and its possible roles.p27在成人前庭感觉器官中的表达及其可能的作用。
Neurosci Lett. 2023 Mar 13;800:137128. doi: 10.1016/j.neulet.2023.137128. Epub 2023 Feb 13.
7
Autophagy Requirements for Eye Lens Differentiation and Transparency.自噬在眼睛晶状体分化和透明性中的作用需求。
Cells. 2023 Feb 1;12(3):475. doi: 10.3390/cells12030475.
8
FOXO transcription factors differ in their dynamics and intra/intermolecular interactions.FOXO转录因子在其动力学以及分子内/分子间相互作用方面存在差异。
Curr Res Struct Biol. 2022 Apr 27;4:118-133. doi: 10.1016/j.crstbi.2022.04.001. eCollection 2022.
9
Targeted regulation of FoxO1 in chondrocytes prevents age-related osteoarthritis via autophagy mechanism.靶向调控软骨细胞中的 FoxO1 通过自噬机制预防与年龄相关的骨关节炎。
J Cell Mol Med. 2022 Jun;26(11):3075-3082. doi: 10.1111/jcmm.17319. Epub 2022 May 13.
10
The role of FYCO1-dependent autophagy in lens fiber cell differentiation.FYCO1 依赖性自噬在晶状体纤维细胞分化中的作用。
Autophagy. 2022 Sep;18(9):2198-2215. doi: 10.1080/15548627.2022.2025570. Epub 2022 Mar 28.