Compositional changes of the lung extracellular matrix in acute respiratory distress syndrome.

IF 5 2区 生物学 Q2 CELL BIOLOGY
YiWen Fan, Jill Moser, Rianne M Jongman, Theo Borghuis, Judith M Vonk, Wim Timens, Matijs van Meurs, Janesh Pillay, Janette K Burgess
{"title":"Compositional changes of the lung extracellular matrix in acute respiratory distress syndrome.","authors":"YiWen Fan, Jill Moser, Rianne M Jongman, Theo Borghuis, Judith M Vonk, Wim Timens, Matijs van Meurs, Janesh Pillay, Janette K Burgess","doi":"10.1152/ajpcell.01007.2024","DOIUrl":null,"url":null,"abstract":"<p><p>Acute respiratory distress syndrome (ARDS) is pathologically characterized by diffuse alveolar damage (DAD) and is associated with high morbidity and mortality rates. Although pulmonary injury initiates alveolar-capillary barrier damage in ARDS, remodeling of the extracellular matrix (ECM), which is pivotal for both tissue repair and organ recovery, may play a large role in persistent ARDS. This study investigated the compositional changes in the ECM in different DAD stages in ARDS. Paraffin-embedded lung sections collected during autopsy or from posttransplant lungs were obtained from patients with ARDS (<i>n</i> = 28) admitted to the University Medical Center Groningen between 2010 and 2020. Sections were stained histochemically, and immunohistochemically for collagen III α1 chain (Col IIIa1), IV α3 chain (Col IVa3), VI α1 chain (Col VIa1), periostin (PSTN), lumican (LUM), and fibronectin (FN). The sections were divided into 118 regions based on DAD stages (54 early vs. 64 advanced). The differences in the expression of selected proteins were compared between DAD stages or across ARDS duration (<7 days, 7-14 days, and >14 days). The fiber pattern of Col VIa1 was analyzed using CellProfiler. Higher tissue density, lower proportional areas of Col IIIa1, Col IVa3, and LUM, and more concentrated Col VIa1 fibers were observed in the advanced DAD stage than in the early DAD stage. Areas with higher proportions of total collagen and FN, and lower proportional areas of Col IIIa1, Col IVa3, and LUM were detected in lung regions from patients with ARDS >14-days duration. These findings revealed proportional changes in ECM components, strongly suggesting that dynamic changes in ECM proteins play a role in pathophysiology in ARDS during progression.<b>NEW & NOTEWORTHY</b> Our study revealed ECM protein compositional differences in lung parenchyma between stages of DAD. In advanced DAD, tissue density was higher, but collagen type III, type IV, and lumican were proportionally lower compared with early DAD. The organization of collagen type VI fibers was highly concentrated in advanced DAD. Our results indicate that both composition and organization of ECM were remodeled in advanced DAD, suggesting a role in manifesting acute respiratory distress syndrome.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C1279-C1292"},"PeriodicalIF":5.0000,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"American journal of physiology. Cell physiology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1152/ajpcell.01007.2024","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/3/10 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Acute respiratory distress syndrome (ARDS) is pathologically characterized by diffuse alveolar damage (DAD) and is associated with high morbidity and mortality rates. Although pulmonary injury initiates alveolar-capillary barrier damage in ARDS, remodeling of the extracellular matrix (ECM), which is pivotal for both tissue repair and organ recovery, may play a large role in persistent ARDS. This study investigated the compositional changes in the ECM in different DAD stages in ARDS. Paraffin-embedded lung sections collected during autopsy or from posttransplant lungs were obtained from patients with ARDS (n = 28) admitted to the University Medical Center Groningen between 2010 and 2020. Sections were stained histochemically, and immunohistochemically for collagen III α1 chain (Col IIIa1), IV α3 chain (Col IVa3), VI α1 chain (Col VIa1), periostin (PSTN), lumican (LUM), and fibronectin (FN). The sections were divided into 118 regions based on DAD stages (54 early vs. 64 advanced). The differences in the expression of selected proteins were compared between DAD stages or across ARDS duration (<7 days, 7-14 days, and >14 days). The fiber pattern of Col VIa1 was analyzed using CellProfiler. Higher tissue density, lower proportional areas of Col IIIa1, Col IVa3, and LUM, and more concentrated Col VIa1 fibers were observed in the advanced DAD stage than in the early DAD stage. Areas with higher proportions of total collagen and FN, and lower proportional areas of Col IIIa1, Col IVa3, and LUM were detected in lung regions from patients with ARDS >14-days duration. These findings revealed proportional changes in ECM components, strongly suggesting that dynamic changes in ECM proteins play a role in pathophysiology in ARDS during progression.NEW & NOTEWORTHY Our study revealed ECM protein compositional differences in lung parenchyma between stages of DAD. In advanced DAD, tissue density was higher, but collagen type III, type IV, and lumican were proportionally lower compared with early DAD. The organization of collagen type VI fibers was highly concentrated in advanced DAD. Our results indicate that both composition and organization of ECM were remodeled in advanced DAD, suggesting a role in manifesting acute respiratory distress syndrome.

急性呼吸窘迫综合征(ARDS)的病理特征是弥漫性肺泡损伤(DAD),发病率和死亡率都很高。细胞外基质(ECM)是组织修复和器官恢复的关键,其重塑可能在持续性 ARDS 中发挥重要作用。本研究调查了 ARDS 不同 DAD 阶段 ECM 的成分变化。研究人员从 2010-2020 年间格罗宁根大学医学中心收治的 ARDS 患者(28 人)身上采集了尸检时或移植后肺部的石蜡包埋肺切片。切片经组织化学染色和免疫组化染色,以检测胶原 III α1链(Col IIIa1)、IV α3链(Col IVa3)、VI α1链(Col VIa1)、骨膜增生蛋白(PSTN)、lumican(LUM)和纤连蛋白(FN)。根据 DAD 阶段(54 个早期与 64 个晚期)将切片分为 118 个区域。比较了不同 DAD 阶段或不同 ARDS 持续时间(14 天)所选蛋白表达的差异。使用 CellProfiler 分析了 Col VIa1 的纤维模式。与 DAD 早期相比,DAD 晚期的组织密度更高,Col IIIa1、Col IVa3 和 LUM 的面积比例更低,Col VIa1 纤维更集中。在病程大于 14 天的 ARDS 患者的肺部区域中,发现了总胶原蛋白和 FN 比例较高,而 Col IIIa1、Col IVa3 和 LUM 比例较低的区域。这些发现揭示了 ECM 成分的比例变化,强烈提示 ECM 蛋白的动态变化在 ARDS 进展过程中的病理生理学中发挥作用。
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
9.10
自引率
1.80%
发文量
252
审稿时长
1 months
期刊介绍: The American Journal of Physiology-Cell Physiology is dedicated to innovative approaches to the study of cell and molecular physiology. Contributions that use cellular and molecular approaches to shed light on mechanisms of physiological control at higher levels of organization also appear regularly. Manuscripts dealing with the structure and function of cell membranes, contractile systems, cellular organelles, and membrane channels, transporters, and pumps are encouraged. Studies dealing with integrated regulation of cellular function, including mechanisms of signal transduction, development, gene expression, cell-to-cell interactions, and the cell physiology of pathophysiological states, are also eagerly sought. Interdisciplinary studies that apply the approaches of biochemistry, biophysics, molecular biology, morphology, and immunology to the determination of new principles in cell physiology are especially welcome.
×
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