American Journal of Respiratory Cell and Molecular Biology最新文献

{"title":"E3 ubiquitin ligases and asthma relief.","authors":"Ajay P Nayak","doi":"10.1165/rcmb.2025-0532ED","DOIUrl":"10.1165/rcmb.2025-0532ED","url":null,"abstract":"","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"280-282"},"PeriodicalIF":5.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12958490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273656","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":"CFTR modulator therapy impacts neutrophil CD39 expression in cystic fibrosis.","authors":"Debananda Gogoi, Claudie Gabillard-Lefort, Rory Baird, Luke Forde, Mengxin Niu, Sara Waqas Ahmed, Cedric Gunaratnam, Michael Williamson, Michelle Casey, Emer P Reeves","doi":"10.1165/rcmb.2025-0262LE","DOIUrl":"10.1165/rcmb.2025-0262LE","url":null,"abstract":"","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"403-406"},"PeriodicalIF":5.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145129791","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":"Entering the ring: circular RNA in pulmonary macrophage antibacterial responses.","authors":"Brian T Campfield","doi":"10.1165/rcmb.2025-0510ED","DOIUrl":"10.1165/rcmb.2025-0510ED","url":null,"abstract":"","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"283-284"},"PeriodicalIF":5.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13105326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273618","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":"Anti-vimentin antibody mitigates SARS-CoV-2 spike protein-induced fibroblast activation and fibrosis.","authors":"Łukasz Suprewicz, Alicja Walewska, Paulina Paprocka, Paul A Janmey, Robert Bucki","doi":"10.1165/rcmb.2025-0124LE","DOIUrl":"10.1165/rcmb.2025-0124LE","url":null,"abstract":"","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"407-410"},"PeriodicalIF":5.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12958411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273643","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":"IRAK2 ubiquitination mediated by PELI1 regulates airway epithelial function and alleviates pediatric asthma.","authors":"Sha Wang, Jinping Ruan, Pan Yan, Linyan Ying","doi":"10.1165/rcmb.2024-0573OC","DOIUrl":"10.1165/rcmb.2024-0573OC","url":null,"abstract":"<p><strong>Rationale: </strong>PELI1, an E3 ubiquitin ligase, has been identified as a controller of the innate immune response.</p><p><strong>Objectives: </strong>This study was designed to expound the functional role of PELI1 in asthma (AS).</p><p><strong>Methods: </strong>Newborn mice were induced with house dust mite (HDM) to establish a mouse model of AS, and overexpression of Peli1 was performed specifically in airway epithelial cells by AAV6.2 vector. The human bronchial epithelial cell line 16HBE was induced with HDM, PELI1 was overexpressed in 16HBE cells by liposome transfection, and knockout was elicited through CRISPR/Cas9.</p><p><strong>Measurements and main results: </strong>Peli1 expression was reduced in the airway epithelium of newborn mice induced with HDM, and overexpression of Peli1 alleviated airway inflammation, mitigated airway injury, and inhibited airway remodeling in AS mice. PELI1 induced protein degradation of IRAK2 through K63 ubiquitination modification. Ectopic expression of Irak2 abated the mitigating effect of Peli1 overexpression on airway inflammation by activating p38-mitogen-activated protein kinase 1 (MAPK)/NF-κB signaling. Blockade of MAPK/NF-κB signaling mitigated the exacerbation of inflammatory responses and cellular damage in 16HBE cells induced by IRAK2 overexpression.</p><p><strong>Conclusions: </strong>Taken together, this research reveals a functional role of PELI1 in IRAK2 degradation and airway inflammation, which provides novel insights into the treatment of pediatric AS.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"311-325"},"PeriodicalIF":5.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145129827","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":"IGF2BP3-mediated NTSR1 m6A methylation enhances irinotecan resistance and lung adenocarcinoma malignant progression.","authors":"Hao Ding, Xuan Zhu, Yongquan Pan, Qi Zhang, Min Feng, Yi Yu, Yueping Fan, Li Zhu","doi":"10.1165/rcmb.2024-0487OC","DOIUrl":"10.1165/rcmb.2024-0487OC","url":null,"abstract":"<p><strong>Rationale: </strong>Neurotensin receptor 1 (NTSR1) is a high-affinity receptor for neurotensin. Its abnormal expression correlates with cancer development. However, its mechanisms in promoting the malignant progression and irinotecan resistance in lung adenocarcinoma (LUAD) remain unelucidated.</p><p><strong>Methods: </strong>NTSR1 expression in LUAD and its relationship with patients' prognosis were analyzed by bioinformatics analysis. NTSR1 expression in a human normal pulmonary epithelial cell line and LUAD cell lines was detected by RT-qPCR and Western blot. Cell proliferation ability was examined using the CCK-8 assay and colony formation assay. Flow cytometry was employed to detect cell cycle and apoptosis. The Transwell assay was undertaken to assess cell migration and invasion ability. DNA damage was detected using the comet assay and γ-H2AX immunofluorescence. Dot-blot and methylated RNA immunoprecipitation-qPCR were employed to examine m6A methylation levels. The interaction between IGF2 mRNA binding protein (IGF2BP3) and NTSR1 was verified by RNA immunoprecipitation and dual luciferase experiments. Immunohistochemistry was applied to analyze protein expression in mouse tumor tissues.</p><p><strong>Measurements and main results: </strong>NTSR1 was upregulated in LUAD cells, affecting patients' dismal overall survival. NTSR1 knockdown hindered cell proliferation, migration, and invasion, and reinforced apoptosis and irinotecan sensitivity. Mechanistically, IGF2BP3 interacted with NTSR1 and induced m6A methylation modification to enhance transcriptional stability, advancing the malignant progression of LUAD and irinotecan resistance. Additionally, NTSR1 knockdown enhanced the sensitivity of LUAD to irinotecan in mice and induced DNA damage.</p><p><strong>Conclusions: </strong>Overall, IGF2BP3-mediated NTSR1 m6A methylation expedites LUAD malignant progression and reinforces irinotecan resistance. Targeting this pathway may be an effective method for treating LUAD.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"364-374"},"PeriodicalIF":5.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145129800","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":"Multi-Omic and Single-Cell Approaches for Elucidating Cell Biology and Pathobiology of Lung Disease.","authors":"Aartik Sarma, Xin Sun, Jennifer Sucre, Jason Hong, Lejla Medzikovic, Claudia V Jakubzick, Xin Li, Rachel L Zemans, Benjamin D Singer","doi":"10.1165/rcmb.2025-0092PS","DOIUrl":"10.1165/rcmb.2025-0092PS","url":null,"abstract":"<p><p>In this Perspective, we review the major themes from a Basic Science Core session at the American Thoracic Society 2024 International Conference: multi-omic and single-cell approaches for elucidating cellular biology and pathobiology of lung disease, with a focus on novel biology identified in human lungs. Recent advances have enabled researchers to study nucleic acids, proteins, and metabolites at single-cell resolution in the lung. These tools can be integrated with complementary methods to lead to new discoveries about lung function and develop treatments for respiratory diseases. We discuss the role of multicenter consortia in developing lung cell atlases and highlight the role of single-cell methods in identifying new respiratory cell types. We then review advances in several respiratory diseases that demonstrate the use of these tools to study lung development, injury, and repair. Finally, we consider future directions for the field, including efforts to harmonize cell types across studies and to develop more robust analytical pipelines.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"287-294"},"PeriodicalIF":5.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12313468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697423","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":"CircMIRLET7BHG facilitates mast cell degranulation to accelerate AR progression by enhancing IL-33 mRNA stability via interacting with PTBP1.","authors":"Jiabin Zhan, Rui Li, Yisen Liang, Dan Luo, Yu Zhou, Xin Wei","doi":"10.1093/ajrcmb/aanag030","DOIUrl":"https://doi.org/10.1093/ajrcmb/aanag030","url":null,"abstract":"<p><p>Mast cell (MC) degranulation is associated with allergic rhinitis (AR) progression. Although circMIRLET7BHG has been identified as a promoter of AR development, its potential regulatory role in MC degranulation during AR progression has not been clarified. To address this, MCs (LAD2) were co-cultured with ovalbumin (OVA)-induced human nasal mucosa epithelial cells (HNEpC), and an AR mouse model was generated through OVA stimulation. The expression levels of circMIRLET7BHG and interleukin-33 (IL-33) were assessed by qRT-PCR, while cytokine production in MCs was quantified using ELISA. MC degranulation was evaluated by toluidine blue staining, and western blotting was employed to detect the expression of polypyrimidine tract-binding protein 1 (PTBP1) and proteins related to mitochondrial fusion and fission. The interactions of PTBP1 with circMIRLET7BHG and IL-33 were verified by RNA immunoprecipitation and RNA pull-down assays, and IL-33 mRNA stability was determined using the actinomycin D assay. Co-culture of LAD2 cells with OVA-induced HNEpC demonstrated that circMIRLET7BHG knockdown inhibited MC degranulation by suppressing mitochondrial fission. Mechanistically, circMIRLET7BHG enhanced IL-33 mRNA stability through its interaction with PTBP1. IL-33 overexpression promoted mitochondrial fission and accelerated MC degranulation, whereas this effect was reversed upon circMIRLET7BHG knockdown. In OVA-induced AR mouse models, circMIRLET7BHG overexpression increased epithelial thickness, eosinophil infiltration, and apoptosis, thereby aggravating allergic symptoms by enhancing mitochondrial fission and MC degranulation via upregulation of IL-33 expression. In conclusion, these findings demonstrate that circMIRLET7BHG promotes AR progression by enhancing mitochondrial fission and MC degranulation through regulation of the PTBP1/IL-33 axis, suggesting a potential novel therapeutic target for AR treatment.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832113","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":"Regional micro-CT analysis enables longitudinal detection of compensatory ventilation effects in a mouse model of pulmonary fibrosis.","authors":"Martina Buccardi, Francesca Pennati, Erica Ferrini, Davide Buseghin, Eugenia Polverini, Nicola Sverzellati, Andrea Aliverti, Franco Fabio Stellari","doi":"10.1093/ajrcmb/aanag036","DOIUrl":"https://doi.org/10.1093/ajrcmb/aanag036","url":null,"abstract":"<p><p>Accurate lung function assessment is essential in preclinical idiopathic pulmonary fibrosis (IPF) research, yet conventional whole-lung endpoints overlook spatial heterogeneity and compensatory mechanisms. We present a µCT-based pipeline for longitudinal, regional quantification of structural and functional changes in a murine bleomycin (BLM)-induced fibrosis model to improve evaluation of disease progression and therapeutic effects. C57BL/6 mice received triple oropharyngeal administrations of saline or BLM. Respiratory-gated µCT scans were acquired in free-breathing at baseline and days 7, 14, and 21. A deep-learning algorithm segmented the lungs into left and right lobes, further subdivided into apical and caudal regions using airway landmarks. Regional volumes, aeration compartments, and ventilation maps were extracted to assess structural and functional alterations. Saline-treated mice showed stable metrics over time, with minimal inter-animal variability, demonstrating the robustness and physiological consistency of our segmentation procedure. BLM-treated animals exhibited early and heterogeneous fibrotic changes, with the apical regions appearing as most affected. The caudal-right region displayed a compensatory functional increase of respiratory parameters derived from multivolume µCT. µCT-based regional analysis can detect localized dysfunction and compensatory effects not captured by whole-lung measurements. This strategy is applicable to different models of heterogeneous lung disease and may contribute to reduce the translational gap in IPF research.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832570","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":"TSG-6 promotes Fascin-1-Mediated Microvascular Repair in Murine Airway Allografts.","authors":"Mohammad Afzal Khan, Dong Ge Li, Subarna Bhusal, Alexander S Krupnick, Christine L Lau","doi":"10.1093/ajrcmb/aanag032","DOIUrl":"https://doi.org/10.1093/ajrcmb/aanag032","url":null,"abstract":"<p><p>Bronchial anastomotic complications, including stenosis, necrosis, and dehiscence, remain major contributors to morbidity and poor graft outcomes following lung transplantation. These complications are primarily driven by microvascular disruption, causing hypoxia, epithelial injury, and impaired wound healing at the anastomosis. Tumor necrosis factor-stimulated gene 6 (TSG-6) protein is a secreted anti-inflammatory mediator with immunomodulatory and tissue-reparative properties; however, its role in transplant-associated vascular and epithelial regeneration remains incompletely defined. In this study, we investigated the therapeutic potential of exogenous TSG-6 in preserving airway microvasculature and promoting immunoregulation in a murine orthotopic tracheal transplant model that mimics the clinical setting of bronchial anastomosis following lung transplantation. BALB/cJ→C57BL/6J allografts were treated intranasally with recombinant TSG-6 (5 µg per transplant) on days -1, 2, 5, and 8 post-transplantation. Exogenous TSG-6 therapy significantly increased the recruitment of M2 macrophages, regulatory T cells, and subsets of regulatory B cells, shifting the graft microenvironment toward an IL-10-dominant anti-inflammatory state. These immunoregulatory effects were accompanied by improved microvascular perfusion, increased Fascin-1 and β-catenin expression in CD31 + endothelial cells, and preservation of epithelial architecture with reduced inflammation and airway lumen narrowing, in contrast to untreated allografts that showed epithelial disruption with dense mononuclear infiltration. These findings suggest that TSG-6 coordinates vascular and epithelial repair after transplantation via IL-10-mediated immunoregulation and Fascin-1-dependent endothelial remodeling. These results highlight TSG-6 as a promising immunoregulatory factor with therapeutic potential to mitigate ischemia-related airway injury and offer a novel strategy for preventing bronchial anastomotic complications following lung transplantation.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832647","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}