American Journal of Respiratory Cell and Molecular Biology最新文献_第8页

Circular RNA-Cacna1d Plays a Critical Role in Sepsis-induced Lung Injury by Sponging microRNA-185-5p. CircRNA-Cacna1d在脓毒症诱发的肺损伤中通过海绵miRNA-185-5p发挥关键作用

IF 5.9 2区医学

American Journal of Respiratory Cell and Molecular Biology Pub Date : 2025-02-01 DOI: 10.1165/rcmb.2024-0067OC

Jiajia Wang, Jinhui Gao, Ling Ding, Xuanzhe Yang, Dong Zheng, Yuanyuan Zeng, Jianjie Zhu, Wei Lei, Cheng Chen, Zeyi Liu, Jian-An Huang

{"title":"Circular RNA-Cacna1d Plays a Critical Role in Sepsis-induced Lung Injury by Sponging microRNA-185-5p.","authors":"Jiajia Wang, Jinhui Gao, Ling Ding, Xuanzhe Yang, Dong Zheng, Yuanyuan Zeng, Jianjie Zhu, Wei Lei, Cheng Chen, Zeyi Liu, Jian-An Huang","doi":"10.1165/rcmb.2024-0067OC","DOIUrl":"10.1165/rcmb.2024-0067OC","url":null,"abstract":"The role of circular RNAs (circRNAs) in sepsis-induced lung injury is not clear. This study investigated the role and molecular mechanism of a novel circRNA in sepsis-induced lung injury and explored its prognostic value in patients with sepsis. In this study, aberrant circRNA expression profiling in lung tissues from mice with sepsis-induced lung injury was analyzed using high-throughput sequencing. circRNA-Cacna1d was verified by qRT-PCR, and its biological function in sepsis-induced lung injury was validated in vitro and in vivo. The interactions among circRNA-Cacna1d, microRNAs (miRNAs), and their downstream genes were verified. Furthermore, the clinical value of circRNA-Cacna1d in peripheral blood from patients with sepsis was also evaluated. We found that circRNA-Cacna1d expression was significantly increased in lung tissues of mice with sepsis and in microvascular endothelial cells after LPS challenge. circRNA-Cacna1d knockdown alleviated inflammatory response and ameliorated the permeability of vascular endothelium, thereby mitigating sepsis-induced lung injury and significantly improving the survival rate of mice with sepsis. Mechanistically, circRNA-Cacna1d directly interacted with miRNA-185-5p and functioned as a miRNA sponge to regulate the RhoA/ROCK1 signaling pathway. The expression level of circRNA-Cacna1d in patients with early sepsis was significantly higher than that in the healthy control subjects. Higher levels of circRNA-Cacna1d in patients with sepsis were associated with increased disease severity and poorer outcomes. In conclusions, circRNA-Cacna1d may play a role in sepsis-induced lung injury by regulating the RhoA/ROCK1 axis by acting as a miRNA-185-5p sponge. circRNA-Cacna1d is a potential therapeutic target for sepsis-induced lung injury and a prognostic biomarker in sepsis.","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"181-194"},"PeriodicalIF":5.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139021","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

Airway Smooth Muscle Dysfunction in Asthma: Releasing the Anchor. 哮喘的气道平滑肌功能障碍：释放锚。

IF 5.9 2区医学

American Journal of Respiratory Cell and Molecular Biology Pub Date : 2025-02-01 DOI: 10.1165/rcmb.2024-0374ED

Anthony N Gerber

引用次数: 0

Targeting Fibrosis in Right Ventricular Pressure Overload: Balancing on a Tightrope? 针对右心室压力超负荷时的纤维化：走钢丝？

IF 5.9 2区医学

American Journal of Respiratory Cell and Molecular Biology Pub Date : 2025-02-01 DOI: 10.1165/rcmb.2024-0377ED

Jessie van Wezenbeek, Frances S de Man

引用次数: 0

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

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

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

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":"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.