American Journal of Respiratory Cell and Molecular Biology最新文献

{"title":"Impact of Canadian Wildfire Smoke Exposure on Nasal Inflammation Markers in New York City Residents.","authors":"Winny Soerianto, Kayla Rae Farrell, Kevin Schichlein, Terry Gordon, Ilona Jaspers","doi":"10.1165/rcmb.2024-0558LE","DOIUrl":"10.1165/rcmb.2024-0558LE","url":null,"abstract":"","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":"73 3","pages":"481-483"},"PeriodicalIF":5.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12416301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144939098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LAM-CAM: <i>In Vivo</i> Model for Rapid Analysis of Lymphangioleiomyomatosis Tumor Formation and Inhibition.","authors":"Nandini Kundu, Alicia Belcher, Julie S Di Martino, Marina K Holz","doi":"10.1165/rcmb.2024-0514LE","DOIUrl":"10.1165/rcmb.2024-0514LE","url":null,"abstract":"","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":"73 3","pages":"479-481"},"PeriodicalIF":5.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12416298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144939084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-Read Sequencing Reveals Tumor-Specific Splicing Isoforms as Therapeutic Targets In NSCLC.","authors":"Yifei Li, Liying Zhou, Hexin Li, Gaoyuan Sun, Siyuan Xu, Xiaokun Tang, Li Wan, Lili Zhang, Min Tang","doi":"10.1165/rcmb.2025-0174OC","DOIUrl":"https://doi.org/10.1165/rcmb.2025-0174OC","url":null,"abstract":"<p><p>Despite extensive transcriptomic alterations observed in tumors, the global landscape of isoform-level alternative splicing in cancer remains largely unexplored. Leveraging long-read sequencing, we successfully identified and characterized full-length isoforms, along with tumor-specific splicing events in non-small cell lung cancer (NSCLC). Our analysis identified 38,058 previously unannotated isoforms, which were subsequently validated using orthogonal multi-omics datasets to confirm their transcriptional and translational activities. Notably, 269 splicing events were characterized as tumor-specific, with 17 showing significant associations with NSCLC subtypes, while 13 were enriched across all NSCLC cases. Among these events, skipped exons in <i>IFI27</i>, <i>PUF60</i> and <i>ANAPC11</i>, as well as an alternative first exon in <i>YBEY</i>, were absent from GENCODE annotations. These findings underscore the intricate complexity of isoforms and their clinical significance, particularly in terms of NSCLC subtype specificity and their potential as therapeutic targets. In conclusion, this study provides a valuable resource for the discovery of tumor-specific splicing targets in NSCLC, leveraging the unique advantages of long-read sequencing.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144939095","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}

{"title":"Role of Metabolic and Inflammatory Mediators from Bronchial Smooth Muscle on Epithelial Infection.","authors":"Benoit Allard","doi":"10.1165/rcmb.2025-0328LE","DOIUrl":"https://doi.org/10.1165/rcmb.2025-0328LE","url":null,"abstract":"","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144939123","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}

{"title":"Capillary Endothelial Cell Subtypes in the Lung: Markers and Response to Developmental Lung Injury.","authors":"Abhijeet Thakur, Geremy Clair, Liang Zhang, Sourabh Soni, Thomas J Mariani, Sule Çataltepe","doi":"10.1165/rcmb.2025-0009OC","DOIUrl":"https://doi.org/10.1165/rcmb.2025-0009OC","url":null,"abstract":"<p><p>Bronchopulmonary dysplasia is a chronic lung disease that affects preterm infants. Disrupted microvascular growth is a well-recognized pathologic feature of BPD, which plays a critical role in arrested alveologenesis. Recent studies have identified two subpopulations of pulmonary microvascular endothelial cells (ECs): general capillary (gCap) and aerocyte (aCap). In this study, we validated proposed markers for gCap (GPIHBP1, PLVAP, CD93) and aCap (CA4, HPGD) at the protein level and investigated their abundance during late-stage lung development in murine and non-human primate (NHP) lungs. We also examined alterations in the abundance and proliferation of gCap and aCap in NHP and murine models of BPD. Our studies confirmed CA4 and HPGD as specific markers for aCap, while all three putative gCap markers were also detected in non-microvascular endothelial cells. All markers, except for HPGD, showed a gradual increase in abundance during the saccular and alveolar stages of development in NHP lungs. In the NHP model of BPD, the abundance of both aCap markers and GPIHBP1 were decreased, while that of PLVAP and CD93 were increased. Additionally, there was an emergence of CA4⁺HPGD^--aCap in BPD lungs. In late-stage control lungs, aCap proliferation was more robust than gCap proliferation, while no significant differences were observed between aCap and gCap proliferation rates in NHP BPD. Notably, in BPD lungs, gCap proliferation was more robust compared to control lungs. This study provides new insights into the distinct regulation patterns of microvascular ECs during lung development and neonatal lung injury in a translationally relevant NHP model.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144939142","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}

{"title":"Chronic Obstructive Pulmonary Disease Airway Epithelial Cell-derived Extracellular Vesicles Spread Cellular Senescence via MicroRNA-34a.","authors":"Justine V Devulder, Jonathan R Baker, Peter S Fenwick, Lina Odqvist, Louise E Donnelly, Peter J Barnes","doi":"10.1165/rcmb.2024-0183OC","DOIUrl":"10.1165/rcmb.2024-0183OC","url":null,"abstract":"<p><p>Chronic obstructive pulmonary disease (COPD) is associated with the acceleration of lung aging and the accumulation of senescent cells in lung tissue. MicroRNA-34a (miR-34a) induces senescence by suppressing the antiaging molecule sirtuin-1 (SIRT1). Senescent cells spread senescence to neighboring and distant cells, favoring COPD progression and its comorbidities. Mechanisms for spreading senescence remain undetermined but may be mediated by the transfer of microRNAs in extracellular vesicles (EVs). We analyzed the microRNA content of EVs in COPD and explored their effect on cellular senescence of healthy cells. EVs were isolated from small airway epithelial cells (SAECs) from healthy donors or patients with COPD. Recipient healthy SAECs were cultured with EVs, and the expression of miR-34a and markers of cellular senescence p21^CIP1 (cyclin-dependent kinase inhibitor-1) and SIRT1 was measured. We have shown that EVs from COPD cells induce senescence in healthy recipient cells via the selective transfer of miR-34a. COPD SAECs produce increased numbers of EVs enriched with miR-34a. EVs are taken up by healthy cells, resulting in reduced expression of the antiaging molecule SIRT1 and increased expression of markers of senescence, such as p21^CIP1 and positive staining for senescence-associated β-galactosidase, which were blocked by a specific miR-34a antagomir. Our findings provide evidence of the mechanism by which EVs spread cellular senescence in human primary cells via miR-34a rather than via soluble mediators. EVs enriched with miR-34a may spread senescence locally, accounting for disease progression, but also provide a mechanism for distant spread to account for comorbidities and multimorbidity in elderly individuals.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"210-220"},"PeriodicalIF":5.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12334839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142997833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Breathing New Life into Pulmonary Arterial Hypertension Treatment: Targeting Serotonin Synthesis with an Inhalation Approach.","authors":"Michael H Lee, Rahul Kumar","doi":"10.1165/rcmb.2025-0040ED","DOIUrl":"10.1165/rcmb.2025-0040ED","url":null,"abstract":"","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"168-169"},"PeriodicalIF":5.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12334879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhalation of the Novel Tryptophan Hydroxylase 1 Inhibitor TPT-004 Alleviates Pulmonary Arterial Hypertension.","authors":"Ekaterina Legchenko, Philippe Chouvarine, Klea Hysko, Fatimunnisa Qadri, Radoslaw Wesolowski, Edgar Specker, Silke Glage, Martin Meier, Katharina Schwarz, Joerg Heineke, Gerhard Pohlmann, Mehmet Ramazanoglu, Michael Bader, Georg Hansmann","doi":"10.1165/rcmb.2024-0365OC","DOIUrl":"10.1165/rcmb.2024-0365OC","url":null,"abstract":"<p><p>Inhaled pharmacotherapies are promising treatment options for patients with pulmonary arterial hypertension (PAH), as they minimize extrapulmonary adverse effects. Recently, we developed a highly specific tryptophan hydroxylase 1 inhibitor (TPHi): TPT-004. We hypothesized that repetitive nose-only inhalation of TPT-004 alleviates PAH and pulmonary vascular remodeling in the Sugen 5416/hypoxia (SuHx) rat model. Male Sprague Dawley rats were divided into three groups: ConNx (control animals kept in room air during the study); SuHx+vehicle (rats injected with the VEGFR2 inhibitor SU5416 and then exposed to chronic hypoxia for 3 weeks, followed by 10 days recovery and subsequent 4 weeks of daily vehicle inhalations; and SuHx+TPHi (SuHx-exposed rats after recovery treated with daily inhalations of the TPH1 inhibitor, TPT-004, for 4 weeks). Closed-chest right-left heart catheterization and cardiac magnetic resonance imaging were performed in spontaneously breathing rats. Histological and mRNA-sequencing analyses were performed on lungs. SuHx-exposed rats had severe PAH, right ventricle (RV) hypertrophy, and RV dilation. In comparison with SuHx-exposed rats, TPHi-treated SuHx rats had significantly lower RV systolic pressure (67.25 vs. 51.47 mm Hg; <i>P</i> < 0.0001), normalized RV end-systolic volume (182.6 vs. 105.1 μl; <i>P</i> < 0.0001), and improved RV ejection fraction by cardiac magnetic resonance imaging (47.9 vs. 66.8%; <i>P</i> < 0.0001). Inhaled TPT-004 did not affect left ventricular (LV) end-diastolic or systemic blood pressure. TPT-004 therapy reversed pulmonary vascular remodeling and alveolar macrophage infiltration. RNA sequencing unraveled TPHi-induced changes in pulmonary gene expression: increased cell adhesion as well as reduced cell motility and migration; suppressed extracellular matrix remodeling; modulated immune response; and suppressed pulmonary vascular remodeling by means of modulating proliferation, apoptosis, and homeostasis. Taken together, TPT-004 is an effective therapeutic PAH agent that does not cause any hemodynamic adverse effects in rodents, and thus, should be tested further towards a clinical phase 1b/phase 2 study in patients with PAH.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"288-298"},"PeriodicalIF":5.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143121730","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}

{"title":"CK1δ Is Implicated in TGF-β1 Activation of Human Lung Myofibroblasts.","authors":"Meina Li, Stephanie S Zhang, Trudi Harris, Qianyu Chen, Alastair G Stewart","doi":"10.1165/rcmb.2024-0421LE","DOIUrl":"10.1165/rcmb.2024-0421LE","url":null,"abstract":"","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"322-325"},"PeriodicalIF":5.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952700","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}

{"title":"Elevated Senescence Markers in Developing Trisomy 21 Human Lungs.","authors":"Randa Belgacemi, Caroline Cherry, Michael Thompson, Maunick Koloko Ngassie, Anika Rehan, Imad El Alam, Claude Jourdan Le Saux, Ian Glass, Rodney D Britt, Y S Prakash, Christina Pabelick, Soula Danopoulos, Denise Al Alam","doi":"10.1165/rcmb.2024-0361OC","DOIUrl":"10.1165/rcmb.2024-0361OC","url":null,"abstract":"<p><p>Human chromosomal anomalies, notably trisomies, disrupt gene expression, leading to diverse cellular and organ phenotypes. Increased cellular senescence (SEN) and oxidative stress in trisomies have gained recent attention. We assessed SEN, SEN-associated secretory phenotype (SASP), and oxidative stress on trisomy 13 (T13), T18, and T21 human fetal lung tissues and isolated primary human fetal lung fibroblasts. Telomerase-associated foci staining showed DNA damage primarily within T21 and T18 lungs. These results were confirmed by real-time quantitative PCR showing an increase of the SEN marker <i>CDKN2B</i> and SASP markers <i>IL-6</i> and <i>CXCL8</i>. In contrast, lung tissues from T13 showed an upregulation of <i>CDKN2A</i>, whereas no significant changes in SASP marker genes were observed. γ-H2AX (H2A histone family member X) was upregulated in each genotype, particularly in T21. Isolated fibroblasts demonstrated a strong association between T21 and several SEN markers. An increase of γ-H2AX-positive cells were observed in fibroblasts from T21, T18, and T13, but only T21 exhibited an increase in P21 expression. Only T21 fibroblasts displayed a significant increase in reactive oxygen species levels, as indicated by MitoSOX and CellROX. This study provides the first evidence of a link between SEN and trisomy anomalies during prenatal human lung development, particularly in T21.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"251-263"},"PeriodicalIF":5.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12334841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143527807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}