American Journal of Respiratory Cell and Molecular Biology最新文献_第2页

Mechanical Stretch Induces Senescence of Lung Epithelial Cells and Drives Fibroblast Activation by Paracrine Mechanisms. 机械拉伸诱导肺上皮细胞衰老并通过旁分泌机制驱动成纤维细胞活化

IF 5.9 2区医学

American Journal of Respiratory Cell and Molecular Biology Pub Date : 2025-02-01 DOI: 10.1165/rcmb.2023-0449OC

Paula Martín-Vicente, Cecilia López-Martínez, Inés López-Alonso, Sara M Exojo-Ramírez, Israel David Duarte-Herrera, Laura Amado-Rodríguez, Irene Ordoñez, Elias Cuesta-Llavona, Juan Gómez, Natalia Campo, Cecilia M O'Kane, Daniel F McAuley, Covadonga Huidobro, Guillermo M Albaiceta

{"title":"Mechanical Stretch Induces Senescence of Lung Epithelial Cells and Drives Fibroblast Activation by Paracrine Mechanisms.","authors":"Paula Martín-Vicente, Cecilia López-Martínez, Inés López-Alonso, Sara M Exojo-Ramírez, Israel David Duarte-Herrera, Laura Amado-Rodríguez, Irene Ordoñez, Elias Cuesta-Llavona, Juan Gómez, Natalia Campo, Cecilia M O'Kane, Daniel F McAuley, Covadonga Huidobro, Guillermo M Albaiceta","doi":"10.1165/rcmb.2023-0449OC","DOIUrl":"10.1165/rcmb.2023-0449OC","url":null,"abstract":"Severe lung injury requiring mechanical ventilation may lead to secondary fibrosis. Senescence, a cell response characterized by cell cycle arrest and a shift toward a proinflammatory/profibrotic phenotype, is one of the involved mechanisms. In this study, we explore the contribution of mechanical stretch as a trigger of senescence of the respiratory epithelium and its link with fibrosis. Human lung epithelial cells and fibroblasts were exposed in vitro to mechanical stretch, and senescence was assessed. In addition, fibroblasts were exposed to culture media preconditioned by senescent epithelial cells, and their activation was studied. Transcriptomic profiles from stretched, senescent epithelial cells and activated fibroblasts were combined to identify potential activated pathways. Finally, the senolytic effects of digoxin were tested in these models. Mechanical stretch induced senescence in lung epithelial cells, but not in fibroblasts. This stretch-induced senescence has specific features compared with senescence induced by doxorubicin. Fibroblasts were activated after exposure to supernatants conditioned by epithelial senescent cells. Transcriptomic analyses revealed Notch signaling as potentially responsible for the epithelial-mesenchymal cross-talk, because blockade of this pathway inhibits fibroblast activation. Treatment with digoxin reduced the percentage of senescent cells after stretch and ameliorated the fibroblast response to preconditioned media. These results suggest that lung fibrosis in response to mechanical stretch may be caused by the paracrine effects of senescent cells. This pathogenetic mechanism can be pharmacologically manipulated to improve lung repair.","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"195-205"},"PeriodicalIF":5.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exposure to Urban Air Pollution Particulate Matter Modifies Th1/Th2 Mtb Immunity in the Human Lung.

IF 5.9 2区医学

American Journal of Respiratory Cell and Molecular Biology Pub Date : 2025-02-01 DOI: 10.1165/rcmb.2024-0240LE

Srijata Sarkar, Claudia Carranza, Yolanda Gonzalez, Junfeng Jim Zhang, Álvaro R Osornio Vargas, Pamela Ohman-Strickland, Martha Torres, Stephan Schwander

引用次数: 0

Endothelialized Bronchioalveolar Lung Organoids Model Endothelial Cell Responses to Injury. 内皮化支气管肺泡有机体模拟内皮细胞对损伤的反应

IF 5.9 2区医学

American Journal of Respiratory Cell and Molecular Biology Pub Date : 2025-02-01 DOI: 10.1165/rcmb.2023-0373MA

Anna-Lena Ament, Monika Heiner, Marie Christin Hessler, Ioannis Alexopoulos, Katharina Steeg, Ulrich Gärtner, Ana Ivonne Vazquez-Armendariz, Susanne Herold

{"title":"Endothelialized Bronchioalveolar Lung Organoids Model Endothelial Cell Responses to Injury.","authors":"Anna-Lena Ament, Monika Heiner, Marie Christin Hessler, Ioannis Alexopoulos, Katharina Steeg, Ulrich Gärtner, Ana Ivonne Vazquez-Armendariz, Susanne Herold","doi":"10.1165/rcmb.2023-0373MA","DOIUrl":"10.1165/rcmb.2023-0373MA","url":null,"abstract":"Organoid three-dimensional systems are powerful platforms to study development and disease. Recently, the complexity of lung organoid models derived from adult mouse and human stem cells has increased substantially in terms of cellular composition and structural complexity. However, a murine lung organoid system with a clear integrated endothelial compartment is still missing. Here, we describe a novel method that adds another level of intricacy to our published bronchioalveolar lung organoid (BALO) model by microinjection of FACS-sorted lung endothelial cells (ECs) into differentiated organoid cultures. Before microinjection, ECs obtained from the lung homogenate of young mice expressed typical EC markers such as CD31 and vascular endothelial cadherin and showed tube formation capacity. Following microinjection, ECs surrounded the BALO's alveolar-like compartment, aligning with type I and type II alveolar epithelial cells, as demonstrated by confocal and electron microscopy. Notably, expression of Car4 and Aplnr was as well detected, suggesting the presence of EC microvascular phenotypes in the cultured ECs. Moreover, upon epithelial cell injury by LPS and influenza A virus, endothelialized BALOs released proinflammatory cytokines, leading to the upregulation ICAM-1 (intercellular adhesion molecule 1) in ECs. In summary, we characterized for the first time an organoid model that incorporates ECs into the alveolar structures of lung organoids, not only increasing our previous model's cellular and structural complexity but also providing a suitable niche to model lung endothelium responses to injury ex vivo.","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"124-132"},"PeriodicalIF":5.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Type I Interferon Targets Alveolar Macrophages to Promote Bacterial Pneumonia after Viral Infection.

IF 5.9 2区医学

American Journal of Respiratory Cell and Molecular Biology Pub Date : 2025-01-29 DOI: 10.1165/rcmb.2024-0552OC

Sunil Palani, Md Bashir Uddin, Michael McKelvey, Shengjun Shao, Wenzhe Wu, Xiaoyong Bao, Jiaren Sun, Keer Sun

{"title":"Type I Interferon Targets Alveolar Macrophages to Promote Bacterial Pneumonia after Viral Infection.","authors":"Sunil Palani, Md Bashir Uddin, Michael McKelvey, Shengjun Shao, Wenzhe Wu, Xiaoyong Bao, Jiaren Sun, Keer Sun","doi":"10.1165/rcmb.2024-0552OC","DOIUrl":"https://doi.org/10.1165/rcmb.2024-0552OC","url":null,"abstract":"Exposure to influenza A virus (IAV), respiratory syncytial virus (RSV), and human metapneumovirus (hMPV) is well-known to increase the risk of Streptococcus pneumoniae (SPn) pneumonia in humans. Type I interferon (IFN-I) is a hallmark response to acute viral infections, and alveolar macrophages (AMs) constitute the first line of airway defense against opportunistic bacteria. Our study reveals that virus-induced IFN-I receptor (IFNAR1) signaling directly impairs AM-dependent antibacterial protection. Using Ifnar1 conditional knockout mouse models, in vivo antibodies, bone marrow chimeric mice, and AM reconstitution, we demonstrate that IFN-I intrinsically targets AMs to drive hypersusceptibility to SPn following IAV infection. Importantly, we show that RSV and hMPV infection induces robust IFN-I signaling in AMs, coinciding with lethal susceptibility to secondary SPn pneumonia. In contrast, seasonal human coronavirus neither induces significant IFN-I signaling in AMs nor immune predisposition to SPn. Therefore, we conclude that IFN-I inhibition of AMs represents a crucial mechanism underlying antibacterial complications following otherwise asymptomatic or mild respiratory viral infections.","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Circulating Back to Blood: Erythrocyte Precursors Put the Brakes on Acute Lung Injury.

IF 5.9 2区医学

American Journal of Respiratory Cell and Molecular Biology Pub Date : 2025-01-23 DOI: 10.1165/rcmb.2024-0632ED

Jourdan E Brune, Anne M Manicone

引用次数: 0

Loss of Iron Regulatory Protein 2 (IRP2) Protects Mice from Lung Inflammation during Bronchoconstriction.

IF 5.9 2区医学

American Journal of Respiratory Cell and Molecular Biology Pub Date : 2025-01-23 DOI: 10.1165/rcmb.2024-0638ED

Patricia P Ogger

引用次数: 0

Bubble Trouble: Epithelial Extracellular Vesicles and Their microRNA Mischief in COPD.

IF 5.9 2区医学

American Journal of Respiratory Cell and Molecular Biology Pub Date : 2025-01-23 DOI: 10.1165/rcmb.2024-0583ED

Isaac Kirubakaran Sundar

引用次数: 0

An Old Dog Performing the Same Old Tricks: The Role of TGF-β Receptor in Tissue Factor Release and Extracellular Vesicle Formation.

IF 5.9 2区医学

American Journal of Respiratory Cell and Molecular Biology Pub Date : 2025-01-23 DOI: 10.1165/rcmb.2024-0627ED

R Chad Wade, Jessy S Deshane

引用次数: 0

The Art(ery) of Contraction: Using Precision Cut Lung Slices to Model Pulmonary Hypertension in ARDS.

IF 5.9 2区医学

American Journal of Respiratory Cell and Molecular Biology Pub Date : 2025-01-23 DOI: 10.1165/rcmb.2024-0603ED

Maria L Ford, Anushka Ruwanpathirana, Rodney D Britt

引用次数: 0

A Functional Variant rs2122031 in ATG7 Is Associated with the Risk of Radiation Pneumonitis.

IF 5.9 2区医学

American Journal of Respiratory Cell and Molecular Biology Pub Date : 2025-01-23 DOI: 10.1165/rcmb.2024-0238OC

Bo Liu, Yulong Yu, Wan Qin, Li Yang, Minxiao Yi, Lingyan Xiao, Yongbiao Huang, Xiao Zhou, Shiying Yu, Yihua Wang, Cong-Yi Wang, Yang Tang, Xianglin Yuan

{"title":"A Functional Variant rs2122031 in ATG7 Is Associated with the Risk of Radiation Pneumonitis.","authors":"Bo Liu, Yulong Yu, Wan Qin, Li Yang, Minxiao Yi, Lingyan Xiao, Yongbiao Huang, Xiao Zhou, Shiying Yu, Yihua Wang, Cong-Yi Wang, Yang Tang, Xianglin Yuan","doi":"10.1165/rcmb.2024-0238OC","DOIUrl":"10.1165/rcmb.2024-0238OC","url":null,"abstract":"Radiation pneumonitis (RP) is characterized by inflammation and is associated with autophagy. However, the relationship between functional genetic variants of autophagy-related genes and radiation pneumonitis remains unknow. In this study we aimed to investigate whether genetic variants of genes involved in autophagy are associated with radiation pneumonitis. Genotyping was conducted on a total of 301 patients for thirteen single nucleotide polymorphisms (SNPs) of 5 genes in the autophagy pathway using MassArray and Sanger sequencing. Two radiation oncologists independently measured the degree of RP by chest X-ray or CT. The multivariate Cox hazard analysis and multiple testing showed that ATG7: rs2122031 GA/GG significantly decreased the risk of RP ≥ grade 3 (HR=0.369, 95% CI: 0.189-0.720, P=0.003, Pc=0.039). Furthermore, qRT-PCR and immunohistochemical analysis demonstrated that the ATG7: rs2122031 AA genotypes were related to decreased expression of ATG7. Loss of autophagy by deletion of ATG7 in fibroblasts or conditional ATG7 knockout mice was proven to increase radiation pneumonitis. Single-cell RNA-seq revealed regulation of autophagy related genes enriched after irradiation stress in conditional ATG7 knockout mice. Our findings indicated that genetic variants of ATG7 were associated with RP and may therefore be used to predict RP before radiotherapy. Loss of ATG7 was also shown to promote RP, which suggested that ATG7 may be an intervention target for RP. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0