• 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

Wnt/β-连环蛋白信号通路刺激结膜干细胞的自我更新，促进角膜结膜化。

Wnt/β-catenin signaling stimulates the self-renewal of conjunctival stem cells and promotes corneal conjunctivalization.

机构信息

Department of Ophthalmology, Dankook University Hospital, Dankook University College of Medicine, Cheonan, Republic of Korea.

Department of Medical Science, Konyang University, Daejeon, Republic of Korea.

出版信息

Exp Mol Med. 2022 Aug;54(8):1156-1164. doi: 10.1038/s12276-022-00823-y. Epub 2022 Aug 16.

DOI:10.1038/s12276-022-00823-y
PMID:35974097
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9440202/
Abstract

Limbal stem cell deficiency causes conjunctivalization characterized by the covering of the corneal surface with conjunctival epithelium. However, the driving force for the encroachment of these conjunctival cells is unclear. Conjunctival stem cells are bipotent stem cells that can proliferate and differentiate into conjunctival epithelial cells and goblet cells to maintain regeneration of the conjunctival epithelium. Here, we show a robust proliferative response of conjunctival stem cells and upregulation of Wnt2b and Wnt3a gene expression in the conjunctivae of mice with induced limbal stem cell deficiency. Topical application of the Wnt/β-catenin signaling activator CHIR resulted in increased proliferation of ΔNp63α-positive stem cells in the basal layers of the bulbar and forniceal conjunctivae and enhanced invasion of conjunctival epithelial and goblet cells into the corneal surface. We also found that in cultures of stem cells isolated from the human conjunctiva, Wnt/β-catenin pathway activation improved the expansion of the ΔNp63α/ABCG2 double-positive cell population by promoting the proliferation and preventing the differentiation of these cells. These expanded stem cells formed a stratified epithelium containing goblet cells under airlift culture conditions. Our data reveal that Wnt/β-catenin signaling contributes to the pathological process of limbal stem cell deficiency by promoting the self-renewal of conjunctival stem cells and suggest that these cells are a driving force in corneal conjunctivalization.

摘要

角膜缘干细胞缺乏导致结膜化，其特征是角膜表面被结膜上皮覆盖。然而，这些结膜细胞侵犯的驱动力尚不清楚。结膜干细胞是具有多能性的干细胞，能够增殖并分化为结膜上皮细胞和杯状细胞，以维持结膜上皮的再生。在这里，我们发现在诱导的角膜缘干细胞缺乏的小鼠的结膜中，结膜干细胞表现出强烈的增殖反应，并且 Wnt2b 和 Wnt3a 基因表达上调。Wnt/β-catenin 信号激活剂 CHIR 的局部应用导致球结膜和穹窿结膜的基底层中 ΔNp63α 阳性干细胞增殖增加，并增强结膜上皮和杯状细胞侵入角膜表面。我们还发现，在从人结膜分离的干细胞培养物中，Wnt/β-catenin 通路的激活通过促进这些细胞的增殖和阻止其分化，改善了 ΔNp63α/ABCG2 双阳性细胞群的扩增。这些扩增的干细胞在气升培养条件下形成含有杯状细胞的分层上皮。我们的数据表明，Wnt/β-catenin 信号通过促进结膜干细胞的自我更新而促进角膜缘干细胞缺乏的病理过程，并提示这些细胞是角膜结膜化的驱动力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63df/9440202/eda78158cf3e/12276_2022_823_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63df/9440202/2b8c22f30b47/12276_2022_823_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63df/9440202/278357e900d6/12276_2022_823_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63df/9440202/0bf801bf2c6a/12276_2022_823_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63df/9440202/44f2c66003e7/12276_2022_823_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63df/9440202/184b276cbf56/12276_2022_823_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63df/9440202/eda78158cf3e/12276_2022_823_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63df/9440202/2b8c22f30b47/12276_2022_823_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63df/9440202/278357e900d6/12276_2022_823_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63df/9440202/0bf801bf2c6a/12276_2022_823_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63df/9440202/44f2c66003e7/12276_2022_823_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63df/9440202/184b276cbf56/12276_2022_823_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63df/9440202/eda78158cf3e/12276_2022_823_Fig6_HTML.jpg

相似文献

1
Wnt/β-catenin signaling stimulates the self-renewal of conjunctival stem cells and promotes corneal conjunctivalization.Wnt/β-连环蛋白信号通路刺激结膜干细胞的自我更新，促进角膜结膜化。
Exp Mol Med. 2022 Aug;54(8):1156-1164. doi: 10.1038/s12276-022-00823-y. Epub 2022 Aug 16.
2
Experimental study of the mechanism of induction of conjunctival goblet cell hyperexpression using CHIR-99021 in vitro.体外使用 CHIR-99021 诱导结膜杯状细胞过度表达的机制的实验研究。
Biochem Biophys Res Commun. 2023 Aug 6;668:104-110. doi: 10.1016/j.bbrc.2023.05.054. Epub 2023 May 23.
3
Limbal stem cell transplantation: an evidence-based analysis.角膜缘干细胞移植：一项基于证据的分析。
Ont Health Technol Assess Ser. 2008;8(7):1-58. Epub 2008 Oct 1.
4
Characterization of ex vivo cultured limbal, conjunctival, and oral mucosal cells: A comparative study with implications in transplantation medicine.体外培养的角膜缘、结膜和口腔黏膜细胞的特性：一项对移植医学有启示意义的比较研究。
Mol Vis. 2015 Jul 31;21:828-45. eCollection 2015.
5
Divergent effects of Wnt/β-catenin signaling modifiers on the preservation of human limbal epithelial progenitors according to culture condition.根据培养条件的不同，Wnt/β-catenin 信号转导调节剂对人角膜缘上皮祖细胞的保存具有不同的作用。
Sci Rep. 2017 Nov 10;7(1):15241. doi: 10.1038/s41598-017-15454-x.
6
Characterization, isolation, expansion and clinical therapy of human corneal epithelial stem/progenitor cells.人角膜上皮干细胞/祖细胞的鉴定、分离、扩增及临床治疗
J Stem Cells. 2014;9(2):79-91.
7
Wnt/β-catenin signaling regulates proliferation of human cornea epithelial stem/progenitor cells.Wnt/β-连环蛋白信号通路调控人眼角膜上皮干/祖细胞的增殖。
Invest Ophthalmol Vis Sci. 2011 Jul 1;52(7):4734-41. doi: 10.1167/iovs.10-6486.
8
Preservation of human limbal epithelial progenitor cells on carbodiimide cross-linked amniotic membrane via integrin-linked kinase-mediated Wnt activation.通过整合素连接激酶介导的 Wnt 激活作用，将人角膜缘上皮祖细胞保存在碳酸二亚胺交联羊膜上。
Acta Biomater. 2016 Feb;31:144-155. doi: 10.1016/j.actbio.2015.11.042. Epub 2015 Nov 26.
9
Modulation of Wnt/BMP pathways during corneal differentiation of hPSC maintains ABCG2-positive LSC population that demonstrates increased regenerative potential.Wnt/BMP 通路在人胚胎干细胞角膜分化过程中的调控维持 ABCG2 阳性 LSC 群体，该群体表现出增强的再生潜能。
Stem Cell Res Ther. 2019 Aug 5;10(1):236. doi: 10.1186/s13287-019-1354-2.
10
Conjunctival transdifferentiation is due to the incomplete removal of limbal basal epithelium.结膜转分化是由于角膜缘基底上皮未完全清除所致。
Invest Ophthalmol Vis Sci. 1990 Sep;31(9):1903-13.

引用本文的文献

1
The Promotion of Cell Proliferation by Food-Derived Bioactive Peptides: Sources and Mechanisms.食物来源的生物活性肽对细胞增殖的促进作用：来源与机制
Metabolites. 2025 Jul 29;15(8):505. doi: 10.3390/metabo15080505.
2
Microenvironment-optimized gastrodin-functionalized scaffolds orchestrate asymmetric division of recruited stem cells in endogenous bone regeneration.微环境优化天麻素功能化支架协调募集干细胞的不对称分裂，促进内源性骨再生。
J Nanobiotechnology. 2024 Nov 20;22(1):722. doi: 10.1186/s12951-024-02886-7.
3
Melittin promotes the proliferation of Schwann cells in hyperglycemic environment by up‑regulating the Crabp2/Wnt/β‑catenin signaling pathway.

本文引用的文献

1
Keratin 13 is a more specific marker of conjunctival epithelium than keratin 19.角蛋白13是比角蛋白19更具特异性的结膜上皮标志物。
Mol Vis. 2011;17:1652-61. Epub 2011 Jun 18.
2
The Pax-6 homeobox gene is expressed throughout the corneal and conjunctival epithelia.Pax-6 同源框基因在整个角膜和结膜上皮中表达。
Invest Ophthalmol Vis Sci. 1997 Jan;38(1):108-20.
3
Label-retaining cells are preferentially located in fornical epithelium: implications on conjunctival epithelial homeostasis.标记保留细胞优先位于穹窿部上皮：对结膜上皮稳态的影响。
蜂毒素通过上调 Crabp2/Wnt/β-连环蛋白信号通路促进高糖环境中施万细胞的增殖。
Mol Med Rep. 2025 Jan;31(1). doi: 10.3892/mmr.2024.13371. Epub 2024 Oct 25.
4
Advancements in Ocular Regenerative Therapies.眼部再生疗法的进展
Biology (Basel). 2023 May 19;12(5):737. doi: 10.3390/biology12050737.
Invest Ophthalmol Vis Sci. 1995 Jan;36(1):236-46.
4
Corneal re-epithelialization from the conjunctiva.结膜来源的角膜再上皮化。
Invest Ophthalmol Vis Sci. 1981 Jul;21(1 Pt 1):135-42.