Collagen VII Is Associated with Airway Remodeling, Honeycombing, and Fibroblast Foci in Usual Interstitial Pneumonia/Idiopathic Pulmonary Fibrosis.

IF 4.7 2区 医学 Q1 PATHOLOGY
Barbora Svobodová, Anna Löfdahl, Måns Kadefors, Salad Mohamed Ali, Oskar Rosmark, Pavan Prabhala, Mattias Magnusson, Hans Brunnström, Sofia Lundin, Göran Dellgren, Catharina Müller, Linda Elowsson, Gunilla Westergren-Thorsson
{"title":"Collagen VII Is Associated with Airway Remodeling, Honeycombing, and Fibroblast Foci in Usual Interstitial Pneumonia/Idiopathic Pulmonary Fibrosis.","authors":"Barbora Svobodová, Anna Löfdahl, Måns Kadefors, Salad Mohamed Ali, Oskar Rosmark, Pavan Prabhala, Mattias Magnusson, Hans Brunnström, Sofia Lundin, Göran Dellgren, Catharina Müller, Linda Elowsson, Gunilla Westergren-Thorsson","doi":"10.1016/j.ajpath.2025.03.013","DOIUrl":null,"url":null,"abstract":"<p><p>Collagen VII is an essential anchoring protein in the basement membrane zone, maintaining the attachment of stratified and pseudostratified epithelia to the underlying interstitial matrix. However, collagen VII is largely unexplored in normal lungs and idiopathic pulmonary fibrosis (IPF), a disease characterized by excessive accumulation of extracellular matrix and aberrant re-epithelialization of fibrotic lung parenchyma. Analysis of collagen VII mRNA and protein in IPF distal lungs demonstrated elevated levels compared with normal lungs. To investigate its cellular source and spatial distribution in lung tissue, immunohistochemistry, RNAscope in situ hybridization, and cell culture experiments in combination with analysis of public transcriptomic data sets were performed. In IPF lungs, collagen VII was abundant in pathologic remodeled airways and honeycomb cysts, associated with increased basal cell populations. In contrast, in the control lungs, collagen VII was mainly localized in larger airways. RNA sequencing data revealed that epithelial basal cells and keratin 5<sup>-</sup>/keratin 17<sup>+</sup> aberrant basaloid cells are the primary sources of COL7A1 expression. Furthermore, COL7A1 expression was found in mesenchymal subsets, and both collagen VII mRNA and protein were observed in fibroblast foci, another histopathologic feature of IPF. In vitro, COL7A1 expression was found to be increased in normal human lung fibroblasts treated with transforming growth factor-β1. These findings suggest that collagen VII could be involved in the process of abnormal re-epithelialization in lung fibrosis.</p>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":" ","pages":""},"PeriodicalIF":4.7000,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"American Journal of Pathology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.ajpath.2025.03.013","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PATHOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Collagen VII is an essential anchoring protein in the basement membrane zone, maintaining the attachment of stratified and pseudostratified epithelia to the underlying interstitial matrix. However, collagen VII is largely unexplored in normal lungs and idiopathic pulmonary fibrosis (IPF), a disease characterized by excessive accumulation of extracellular matrix and aberrant re-epithelialization of fibrotic lung parenchyma. Analysis of collagen VII mRNA and protein in IPF distal lungs demonstrated elevated levels compared with normal lungs. To investigate its cellular source and spatial distribution in lung tissue, immunohistochemistry, RNAscope in situ hybridization, and cell culture experiments in combination with analysis of public transcriptomic data sets were performed. In IPF lungs, collagen VII was abundant in pathologic remodeled airways and honeycomb cysts, associated with increased basal cell populations. In contrast, in the control lungs, collagen VII was mainly localized in larger airways. RNA sequencing data revealed that epithelial basal cells and keratin 5-/keratin 17+ aberrant basaloid cells are the primary sources of COL7A1 expression. Furthermore, COL7A1 expression was found in mesenchymal subsets, and both collagen VII mRNA and protein were observed in fibroblast foci, another histopathologic feature of IPF. In vitro, COL7A1 expression was found to be increased in normal human lung fibroblasts treated with transforming growth factor-β1. These findings suggest that collagen VII could be involved in the process of abnormal re-epithelialization in lung fibrosis.

在通常的间质性肺炎/特发性肺纤维化中,VII型胶原与气道重塑、蜂窝状和成纤维细胞灶相关
VII型胶原是基底膜区必不可少的锚定蛋白,维持层状上皮和假层状上皮与下层间质基质的附着。然而,VII型胶原蛋白在正常肺和特发性肺纤维化(IPF)中未被广泛研究,IPF是一种以细胞外基质过度积累和纤维化肺实质异常再上皮化为特征的疾病。与正常肺相比,IPF远端肺中胶原VII mRNA和蛋白水平升高。为了研究其在肺组织中的细胞来源和空间分布,我们进行了免疫组织化学、RNAscope原位杂交和细胞培养实验,并结合公开转录组数据集的分析。在IPF肺中,病理重塑的气道和蜂窝囊肿中富含胶原VII,与基底细胞群增加有关。相比之下,在对照肺中,胶原VII主要局限于较大的气道。RNA测序数据显示,上皮基底细胞和角蛋白5-/角蛋白17+异常基底细胞是COL7A1表达的主要来源。此外,COL7A1在间充质亚群中表达,胶原VII mRNA和蛋白在成纤维细胞灶中均可见,这是IPF的另一个组织病理学特征。在体外,经转化生长因子-β1处理的正常人肺成纤维细胞中COL7A1的表达增加。这些结果提示,VII型胶原可能参与了肺纤维化异常再上皮化的过程。
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 求助全文
来源期刊
CiteScore
11.40
自引率
0.00%
发文量
178
审稿时长
30 days
期刊介绍: The American Journal of Pathology, official journal of the American Society for Investigative Pathology, published by Elsevier, Inc., seeks high-quality original research reports, reviews, and commentaries related to the molecular and cellular basis of disease. The editors will consider basic, translational, and clinical investigations that directly address mechanisms of pathogenesis or provide a foundation for future mechanistic inquiries. Examples of such foundational investigations include data mining, identification of biomarkers, molecular pathology, and discovery research. Foundational studies that incorporate deep learning and artificial intelligence are also welcome. High priority is given to studies of human disease and relevant experimental models using molecular, cellular, and organismal approaches.
×
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:604180095
Book学术官方微信