eIF6 modulates skin wound healing by upregulating keratin 6B.

IF 5.4 2区 医学 Q1 CELL & TISSUE ENGINEERING Stem Cells Translational Medicine Pub Date : 2024-11-12 DOI:10.1093/stcltm/szae064
Xiaoyan Wang, Guangchao Xu, Fangyingnan Zhang, Yating Wei, Jiawen Deng, Lan Mu, Jinqing He, Dehua He, Meifang Yin, Ilaria Dal Pra, Xiaofang Liu, Weichao Cai, Linjing Yang, Chunmao Han, Guangtao Huang, Jun Wu
{"title":"eIF6 modulates skin wound healing by upregulating keratin 6B.","authors":"Xiaoyan Wang, Guangchao Xu, Fangyingnan Zhang, Yating Wei, Jiawen Deng, Lan Mu, Jinqing He, Dehua He, Meifang Yin, Ilaria Dal Pra, Xiaofang Liu, Weichao Cai, Linjing Yang, Chunmao Han, Guangtao Huang, Jun Wu","doi":"10.1093/stcltm/szae064","DOIUrl":null,"url":null,"abstract":"<p><p>Eukaryotic translation initiation factor 6 (eIF6) plays a crucial role in 60S ribosome biogenesis and protein translation, as well as in hypertrophic scar formation, but its potential role in epithelialization is still poorly understood. Herein, we found that eIF6 negatively correlated with the wound healing process. Mice with genetically knockdown eIF6 (eIF6+/-) showed faster re-epithelization as shown by the longer tongue of the newly formed epidermis. Furthermore, eIF6 ablation accelerated the wound healing process by targeting basal keratinocytes in the eIF6 keratinocyte-conditional knockout (eIF6f/+; Krt5-Cre+) mice. Mechanistically, keratin 6B, an important wound-activated protein, was significantly upregulated in eIF6f/+; Krt5-Cre+ mice skin as proved by RNA-seq, western immunoblots, and immunofluorescence staining. Moreover, an elevated level of KRT6B and accelerated proliferative capacity were also observed in stable knockdown eIF6 HaCaT cells. Taken together, eIF6 downregulation could accelerate epithelialization by upregulating KRT6B expression and promoting keratinocyte proliferation. Our results for the first time indicate that eIF6 might be a novel target to regulate re-epithelialization.</p>","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":null,"pages":null},"PeriodicalIF":5.4000,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Stem Cells Translational Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/stcltm/szae064","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL & TISSUE ENGINEERING","Score":null,"Total":0}
引用次数: 0

Abstract

Eukaryotic translation initiation factor 6 (eIF6) plays a crucial role in 60S ribosome biogenesis and protein translation, as well as in hypertrophic scar formation, but its potential role in epithelialization is still poorly understood. Herein, we found that eIF6 negatively correlated with the wound healing process. Mice with genetically knockdown eIF6 (eIF6+/-) showed faster re-epithelization as shown by the longer tongue of the newly formed epidermis. Furthermore, eIF6 ablation accelerated the wound healing process by targeting basal keratinocytes in the eIF6 keratinocyte-conditional knockout (eIF6f/+; Krt5-Cre+) mice. Mechanistically, keratin 6B, an important wound-activated protein, was significantly upregulated in eIF6f/+; Krt5-Cre+ mice skin as proved by RNA-seq, western immunoblots, and immunofluorescence staining. Moreover, an elevated level of KRT6B and accelerated proliferative capacity were also observed in stable knockdown eIF6 HaCaT cells. Taken together, eIF6 downregulation could accelerate epithelialization by upregulating KRT6B expression and promoting keratinocyte proliferation. Our results for the first time indicate that eIF6 might be a novel target to regulate re-epithelialization.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
eIF6 通过上调角蛋白 6B 调节皮肤伤口愈合。
真核生物翻译起始因子 6(eIF6)在 60S 核糖体生物发生和蛋白质翻译以及增生性疤痕形成过程中起着至关重要的作用,但其在上皮化过程中的潜在作用仍鲜为人知。在这里,我们发现 eIF6 与伤口愈合过程呈负相关。基因敲除 eIF6(eIF6+/-)的小鼠表现出更快的再上皮化,这表现在新形成的表皮舌头更长。此外,eIF6角质形成细胞条件性敲除(eIF6f/+;Krt5-Cre+)小鼠通过靶向基底角质形成细胞消融加速了伤口愈合过程。RNA-seq、Western 免疫印迹和免疫荧光染色证明,在 eIF6f/+; Krt5-Cre+ 小鼠皮肤中,重要的伤口激活蛋白角蛋白 6B 被显著上调。此外,在稳定敲除 eIF6 的 HaCaT 细胞中也观察到 KRT6B 水平升高和增殖能力加快。综上所述,下调 eIF6 可通过上调 KRT6B 的表达和促进角质形成细胞的增殖来加速上皮化。我们的研究结果首次表明,eIF6 可能是调控上皮再形成的一个新靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
Stem Cells Translational Medicine
Stem Cells Translational Medicine CELL & TISSUE ENGINEERING-
CiteScore
12.90
自引率
3.30%
发文量
140
审稿时长
6-12 weeks
期刊介绍: STEM CELLS Translational Medicine is a monthly, peer-reviewed, largely online, open access journal. STEM CELLS Translational Medicine works to advance the utilization of cells for clinical therapy. By bridging stem cell molecular and biological research and helping speed translations of emerging lab discoveries into clinical trials, STEM CELLS Translational Medicine will help move applications of these critical investigations closer to accepted best patient practices and ultimately improve outcomes. The journal encourages original research articles and concise reviews describing laboratory investigations of stem cells, including their characterization and manipulation, and the translation of their clinical aspects of from the bench to patient care. STEM CELLS Translational Medicine covers all aspects of translational cell studies, including bench research, first-in-human case studies, and relevant clinical trials.
期刊最新文献
Progranulin enhances the engraftment of transplanted human iPS cell-derived cerebral neurons. eIF6 modulates skin wound healing by upregulating keratin 6B. Impact of immunosuppressive drugs on efficacy of mesenchymal stem cell therapy for suppressing renal fibrosis. Mesenchymal stromal cells-derived small extracellular vesicles protect against UV-induced photoaging via regulating pregnancy zone protein. Nose-to-brain delivery of stem cells in stroke: the role of extracellular vesicles.
×
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
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 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 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1