重组 Slit2 通过抑制 TGF-β1/Smad3 信号通路,减轻良性中央气道阻塞中气管成纤维细胞的活化。

IF 2.3 3区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS
Chunyan He , Lei Gu , Anmao Li , Yishi Li , Rui Xiao , Jiaxin Liao , Junhao Mu , Yiling Gan , Mingyu Peng , Giri Mohan , Wei Liu , Li Xu , Shuliang Guo
{"title":"重组 Slit2 通过抑制 TGF-β1/Smad3 信号通路,减轻良性中央气道阻塞中气管成纤维细胞的活化。","authors":"Chunyan He ,&nbsp;Lei Gu ,&nbsp;Anmao Li ,&nbsp;Yishi Li ,&nbsp;Rui Xiao ,&nbsp;Jiaxin Liao ,&nbsp;Junhao Mu ,&nbsp;Yiling Gan ,&nbsp;Mingyu Peng ,&nbsp;Giri Mohan ,&nbsp;Wei Liu ,&nbsp;Li Xu ,&nbsp;Shuliang Guo","doi":"10.1016/j.mcp.2023.101947","DOIUrl":null,"url":null,"abstract":"<div><p>Airway fibrosis is among the pathological manifestations of benign central airway obstruction noted in the absence of effective treatments and requires new drug targets to be developed. Slit guidance ligand 2–roundabout guidance receptor 1 (Slit2–Robo1) is involved in fibrosis and organ development. However, its significance in airway fibrosis has not yet been reported. The study explored how the recombinant protein Slit2 functions in transforming growth factor-β1 (TGF-β1)-mediated airway fibrosis <em>in vivo</em> and <em>in vitro</em>. In this study, Slit2 expression initially increased in the tracheal granulation tissues of patients with tracheobronchial stenosis but decreased in the fibrotic tissue. In primary rat tracheal fibroblasts (RTFs), recombinant Slit2 inhibited the expression of extracellular matrices such as Timp1, α-SMA, and COL1A2, whereas recombinant TGF-β1 promoted the expression of Robo1, α-SMA, and COL1A2. Slit2 and TGF-β1 played a mutual inhibitory role in RTFs. Slit2 supplementation and Robo1 downregulation inhibited excessive extracellular matrix (ECM) deposition induced by TGF-β1 in RTFs via the TGF-β1/Smad3 pathway. Ultimately, exogenous Slit2 and Robo1 knockdown-mediated attenuation of airway fibrosis were validated in a trauma-induced rat airway obstruction model. These findings demonstrate that recombinant Slit2 alleviated pathologic tracheobronchial healing by attenuating excessive ECM deposition. Slit2–Robo1 is an attractive target for further exploring the mechanisms and treatment of benign central airway obstruction.</p></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"73 ","pages":"Article 101947"},"PeriodicalIF":2.3000,"publicationDate":"2023-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0890850823000567/pdfft?md5=cce6971073619e405574862ce424cc36&pid=1-s2.0-S0890850823000567-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Recombinant Slit2 attenuates tracheal fibroblast activation in benign central airway obstruction by inhibiting the TGF-β1/Smad3 signaling pathway\",\"authors\":\"Chunyan He ,&nbsp;Lei Gu ,&nbsp;Anmao Li ,&nbsp;Yishi Li ,&nbsp;Rui Xiao ,&nbsp;Jiaxin Liao ,&nbsp;Junhao Mu ,&nbsp;Yiling Gan ,&nbsp;Mingyu Peng ,&nbsp;Giri Mohan ,&nbsp;Wei Liu ,&nbsp;Li Xu ,&nbsp;Shuliang Guo\",\"doi\":\"10.1016/j.mcp.2023.101947\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Airway fibrosis is among the pathological manifestations of benign central airway obstruction noted in the absence of effective treatments and requires new drug targets to be developed. Slit guidance ligand 2–roundabout guidance receptor 1 (Slit2–Robo1) is involved in fibrosis and organ development. However, its significance in airway fibrosis has not yet been reported. The study explored how the recombinant protein Slit2 functions in transforming growth factor-β1 (TGF-β1)-mediated airway fibrosis <em>in vivo</em> and <em>in vitro</em>. In this study, Slit2 expression initially increased in the tracheal granulation tissues of patients with tracheobronchial stenosis but decreased in the fibrotic tissue. In primary rat tracheal fibroblasts (RTFs), recombinant Slit2 inhibited the expression of extracellular matrices such as Timp1, α-SMA, and COL1A2, whereas recombinant TGF-β1 promoted the expression of Robo1, α-SMA, and COL1A2. Slit2 and TGF-β1 played a mutual inhibitory role in RTFs. Slit2 supplementation and Robo1 downregulation inhibited excessive extracellular matrix (ECM) deposition induced by TGF-β1 in RTFs via the TGF-β1/Smad3 pathway. Ultimately, exogenous Slit2 and Robo1 knockdown-mediated attenuation of airway fibrosis were validated in a trauma-induced rat airway obstruction model. These findings demonstrate that recombinant Slit2 alleviated pathologic tracheobronchial healing by attenuating excessive ECM deposition. Slit2–Robo1 is an attractive target for further exploring the mechanisms and treatment of benign central airway obstruction.</p></div>\",\"PeriodicalId\":49799,\"journal\":{\"name\":\"Molecular and Cellular Probes\",\"volume\":\"73 \",\"pages\":\"Article 101947\"},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2023-12-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S0890850823000567/pdfft?md5=cce6971073619e405574862ce424cc36&pid=1-s2.0-S0890850823000567-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular and Cellular Probes\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0890850823000567\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"BIOCHEMICAL RESEARCH METHODS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular and Cellular Probes","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0890850823000567","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
引用次数: 0

摘要

气道纤维化是良性中央气道阻塞的病理表现之一,由于缺乏有效的治疗方法,需要开发新的药物靶点。裂隙引导配体 2-迂回引导受体 1(Slit2-Robo1)参与纤维化和器官发育。然而,其在气道纤维化中的意义尚未见报道。该研究探讨了重组蛋白Slit2如何在体内和体外转化生长因子-β1(TGF-β1)介导的气道纤维化中发挥作用。在这项研究中,Slit2最初在气管支气管狭窄患者的气管肉芽组织中表达增加,但在纤维化组织中表达减少。在原代大鼠气管成纤维细胞(RTFs)中,重组 Slit2 可抑制 Timp1、α-SMA 和 COL1A2 等细胞外基质的表达,而重组 TGF-β1 可促进 Robo1、α-SMA 和 COL1A2 的表达。Slit2和TGF-β1在RTFs中起着相互抑制的作用。补充 Slit2 和下调 Robo1 可通过 TGF-β1/Smad3 通路抑制 TGF-β1 在 RTFs 中诱导的细胞外基质(ECM)过度沉积。最终,外源性 Slit2 和 Robo1 敲除介导的气道纤维化减轻作用在创伤诱导的大鼠气道阻塞模型中得到了验证。这些研究结果表明,重组 Slit2 可通过减少 ECM 过度沉积而减轻气管支气管的病理愈合。Slit2-Robo1 是进一步探索良性中央气道阻塞的机制和治疗的一个有吸引力的靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Recombinant Slit2 attenuates tracheal fibroblast activation in benign central airway obstruction by inhibiting the TGF-β1/Smad3 signaling pathway

Airway fibrosis is among the pathological manifestations of benign central airway obstruction noted in the absence of effective treatments and requires new drug targets to be developed. Slit guidance ligand 2–roundabout guidance receptor 1 (Slit2–Robo1) is involved in fibrosis and organ development. However, its significance in airway fibrosis has not yet been reported. The study explored how the recombinant protein Slit2 functions in transforming growth factor-β1 (TGF-β1)-mediated airway fibrosis in vivo and in vitro. In this study, Slit2 expression initially increased in the tracheal granulation tissues of patients with tracheobronchial stenosis but decreased in the fibrotic tissue. In primary rat tracheal fibroblasts (RTFs), recombinant Slit2 inhibited the expression of extracellular matrices such as Timp1, α-SMA, and COL1A2, whereas recombinant TGF-β1 promoted the expression of Robo1, α-SMA, and COL1A2. Slit2 and TGF-β1 played a mutual inhibitory role in RTFs. Slit2 supplementation and Robo1 downregulation inhibited excessive extracellular matrix (ECM) deposition induced by TGF-β1 in RTFs via the TGF-β1/Smad3 pathway. Ultimately, exogenous Slit2 and Robo1 knockdown-mediated attenuation of airway fibrosis were validated in a trauma-induced rat airway obstruction model. These findings demonstrate that recombinant Slit2 alleviated pathologic tracheobronchial healing by attenuating excessive ECM deposition. Slit2–Robo1 is an attractive target for further exploring the mechanisms and treatment of benign central airway obstruction.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Molecular and Cellular Probes
Molecular and Cellular Probes 生物-生化研究方法
CiteScore
6.80
自引率
0.00%
发文量
52
审稿时长
16 days
期刊介绍: MCP - Advancing biology through–omics and bioinformatic technologies wants to capture outcomes from the current revolution in molecular technologies and sciences. The journal has broadened its scope and embraces any high quality research papers, reviews and opinions in areas including, but not limited to, molecular biology, cell biology, biochemistry, immunology, physiology, epidemiology, ecology, virology, microbiology, parasitology, genetics, evolutionary biology, genomics (including metagenomics), bioinformatics, proteomics, metabolomics, glycomics, and lipidomics. Submissions with a technology-driven focus on understanding normal biological or disease processes as well as conceptual advances and paradigm shifts are particularly encouraged. The Editors welcome fundamental or applied research areas; pre-submission enquiries about advanced draft manuscripts are welcomed. Top quality research and manuscripts will be fast-tracked.
×
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
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
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 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信