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以促血管生成的COL15A1 + 内皮细胞为特征的肺纤维化疾病和肺腺癌中肺血管的异位扩张。

Ectopic Expansion of Pulmonary Vasculature in Fibrotic Lung Disease and Lung Adenocarcinoma Marked by Proangiogenic COL15A1+ Endothelial Cells.

作者信息

Engelbrecht Eric, Kooistra Tristan, Burg Nathalie, Hariri Lida, Nguyen Trong, Brazee Patricia, Hla Timothy, Gochuico Bernadette R, Knipe Rachel S

机构信息

University of Louisville School of Medicine Louisville Kentucky USA.

Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital Harvard Medical School Boston Massachusetts USA.

出版信息

Pulm Circ. 2025 Jun 3;15(2):e70102. doi: 10.1002/pul2.70102. eCollection 2025 Apr.


DOI:10.1002/pul2.70102
PMID:40463493
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12130637/
Abstract

Lung vasculature arises from both pulmonary and systemic (bronchial) circulations. Remodeling and structural changes in lung vasculature have been recognized in end-stage fibrotic lung diseases such as idiopathic pulmonary fibrosis (IPF) but have not been well characterized. The vasculature that expands and supplies lung cancers is better described, with the recent recognition that systemic bronchial circulation expands to be the main blood supply to primary lung tumors. Here, we use publicly available single-cell RNA-sequencing (scRNA-seq) data to compare vascular endothelial cell (EC) populations in multiple progressive interstitial lung diseases (ILD) and non-small cell lung cancer (NSCLC) to identify common and distinct features. Lung tissue specimens were collected from healthy lung tissue (= 59), ILD (= 97), chronic obstructive pulmonary disease (= 22), and NSCLC (= 8). We identify two subtypes of expanded EC populations in both ILD and NSCLC, "Bronch-1" and "Bronch-2", expressing transcripts associated with venules and angiogenic tip/stalk cells, respectively. Relative to pulmonary capillary and arterial ECs, bronchial ECs show low expression of transcripts associated with vascular barrier integrity. The pan-bronchial EC marker COL15A1 showed positive staining in lung parenchyma from patients with IPF, SSc-ILD, and NSCLC, whereas positive staining was limited to subpleural and peri-bronchial regions in non-fibrotic controls. In conclusion, expansion of a subset of ECs expressing markers of the bronchial circulation is one of the most pronounced changes in vascular cell composition across multiple ILDs and NSCLC. These data support additional studies to determine the role of the bronchial vasculature in ILD progression.

摘要

肺血管系统起源于肺循环和体循环(支气管循环)。终末期纤维化肺病如特发性肺纤维化(IPF)中肺血管系统的重塑和结构变化已得到认可,但尚未得到充分描述。对扩张并为肺癌供血的血管系统有了更好的描述,最近认识到体循环支气管循环扩张成为原发性肺肿瘤的主要血液供应。在这里,我们使用公开可用的单细胞RNA测序(scRNA-seq)数据来比较多种进行性间质性肺病(ILD)和非小细胞肺癌(NSCLC)中的血管内皮细胞(EC)群体,以识别共同和不同的特征。从健康肺组织(=59例)、ILD(=97例)、慢性阻塞性肺疾病(=22例)和NSCLC(=8例)中收集肺组织标本。我们在ILD和NSCLC中均鉴定出两种扩张的EC群体亚型,即“支气管-1”和“支气管-2”,分别表达与小静脉和血管生成顶端/柄细胞相关的转录本。相对于肺毛细血管和动脉EC,支气管EC显示出与血管屏障完整性相关转录本的低表达。泛支气管EC标志物COL15A1在IPF、系统性硬化症相关ILD和NSCLC患者的肺实质中呈阳性染色,而在非纤维化对照中阳性染色仅限于胸膜下和支气管周围区域。总之,表达支气管循环标志物的EC亚群的扩张是多种ILD和NSCLC中血管细胞组成最显著的变化之一。这些数据支持进一步研究以确定支气管血管系统在ILD进展中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ddc/12130637/f23e36320216/PUL2-15-e70102-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ddc/12130637/3753acac3a6b/PUL2-15-e70102-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ddc/12130637/cb13d54710b2/PUL2-15-e70102-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ddc/12130637/bdb9fff1105e/PUL2-15-e70102-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ddc/12130637/08578c5628f8/PUL2-15-e70102-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ddc/12130637/f23e36320216/PUL2-15-e70102-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ddc/12130637/3753acac3a6b/PUL2-15-e70102-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ddc/12130637/cb13d54710b2/PUL2-15-e70102-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ddc/12130637/bdb9fff1105e/PUL2-15-e70102-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ddc/12130637/08578c5628f8/PUL2-15-e70102-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ddc/12130637/f23e36320216/PUL2-15-e70102-g005.jpg

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本文引用的文献

[1]
Spatial transcriptomics identifies molecular niche dysregulation associated with distal lung remodeling in pulmonary fibrosis.

Nat Genet. 2025-3

[2]
Vascular involvement in idiopathic pulmonary fibrosis.

ERJ Open Res. 2024-11-25

[3]
Efficacy and Safety of Admilparant, an LPA Antagonist, in Pulmonary Fibrosis: A Phase 2 Randomized Clinical Trial.

Am J Respir Crit Care Med. 2025-2

[4]
Immune mechanisms in fibrotic interstitial lung disease.

Cell. 2024-7-11

[5]
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Am J Respir Crit Care Med. 2024-8-15

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JAMA. 2024-8-6

[7]
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BMC Pulm Med. 2024-3-20

[8]
A small-molecule TNIK inhibitor targets fibrosis in preclinical and clinical models.

Nat Biotechnol. 2025-1

[9]
Ex vivo tissue perturbations coupled to single-cell RNA-seq reveal multilineage cell circuit dynamics in human lung fibrogenesis.

Sci Transl Med. 2023-12-6

[10]
Emerging role of immune cells as drivers of pulmonary fibrosis.

Pharmacol Ther. 2023-12

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