American Journal of Respiratory Cell and Molecular Biology最新文献

{"title":"Combined inhibition of FABP4/5 ameliorates pulmonary hypertension by reducing pulmonary vascular and right ventricular fibrosis.","authors":"Juan Li, Yi Shen, Xi Qiu, Xiaojin Lin, Jiahao He, Ni Ren, Jianuo Yang, Guanli Wang, Zhanjie Mo, Dakai Xiao, Chunli Liu","doi":"10.1165/rcmb.2024-0352OC","DOIUrl":"10.1165/rcmb.2024-0352OC","url":null,"abstract":"<p><strong>Rationale: </strong>Lipid metabolism disorder is increasingly recognized as hallmarks of pulmonary hypertension (PH). Fatty acid-binding proteins (FABPs), particularly FABP4 and FABP5, which regulate lipid transport and metabolism of fatty acid, are thought to contribute to the development of PH. However, it remains unclear whether FABP4 and FABP5 serve as therapeutic targets for the treatment of PH. Measurements and Main.</p><p><strong>Results: </strong>The levels of FABP4/5 were elevated in the plasma and lung tissues of idiopathic pulmonary arterial hypertension (IPAH) patients, as well as in the lung tissues of the PH rat model compared with control. The circulating levels of FABP4 of IPAH patients were correlated with mean pulmonary arterial pressure (mPAP). To determine the preventive or therapeutic effect of FABP4 and FABP5 inhibition, FABP4 and FABP5 inhibitors alone or combination were administered at early (days 2 following monocrotaline [MCT] injection) and late (day 12 following MCT injection) stage of PH rat model, respectively. Combined treatment with FABP4/5 inhibitors in the early stage of the MCT-PH rat model effectively reduced right ventricular systolic pressure (RVSP) and improved right ventricular (RV) function, accompanied by reductions in pulmonary vascular and RV fibrosis, as well as blood lipid levels, lipid peroxidation, and inflammation. Combined treatment with FABP4/5 inhibitors at the late stage of MCT-PH improved RV function, suppressed pulmonary vascular and RV fibrosis, and lowered blood lipid levels, but did not affect RVSP.</p><p><strong>Conclusions: </strong>Combined inhibition of FABP4 and FABP5 can prevent the pathogenesis of PH, representing a potential therapeutic strategy for PH. p.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"466-479"},"PeriodicalIF":5.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145290727","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":"Integrated longitudinal transcriptomic and proteomic analysis of the murine lung response to influenza a virus.","authors":"Tim Flerlage, David F Boyd, Brandi Clark, Nikhil G Marudai, Shally Saini, Cliff Guy, Kristine Pobre-Piza, Jeremy Chase Crawford, Suresh Poudel, Anthony A High, Suiping Zhou, Xusheng Wang, Sherri Surman, Bart Jones, Charles W Frevert, Paul G Thomas","doi":"10.1165/rcmb.2024-0405OC","DOIUrl":"10.1165/rcmb.2024-0405OC","url":null,"abstract":"<p><strong>Rationale: </strong>Lung injury caused by influenza is a leading cause of respiratory infection-related morbidity and mortality worldwide. In its severe form, influenza can cause acute respiratory distress syndrome (ARDS), which manifests as severe hypoxemic respiratory failure. Survivors of the acute stage of ARDS may develop lung fibrosis. The mechanisms underlying fibrotic responses in this context are unknown.</p><p><strong>Objectives: </strong>In this study, we investigate fibroblast responses to influenza challenge.</p><p><strong>Methods: </strong>We used single cell gene expression (scGEX) and two-dimensional liquid chromatography coupled with tandem/mass spectrometry (TMT-LC/LC-MS/MS) on lung tissue collected longitudinally in a murine model of influenza A virus (IAV) infection.</p><p><strong>Measurements and main results: </strong>By TMT-LC/LC-MS/MS, we identified profound changes in the composition of the lung matrisome, which were most evident 10 days after infection. In this context, we identified transcriptional heterogeneity amongst proximal/adventitial fibroblasts expressing Pi16 and Col15a1 as well as a myofibroblast activation state characterized by expression of Tnc, Spp1, Grem1, and Cthrc1. This activation state was transcriptionally similar to those previously described in other contexts.</p><p><strong>Conclusions: </strong>Together, these data suggest compartmentalization and conservation of pulmonary fibroblast responses to lung injury of different primary etiologies.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"480-496"},"PeriodicalIF":5.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273648","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":"SART3 activates CD36 transcription by recruiting FOXM1 and activates PARP to augment cisplatin resistance in non-small cell lung cancer.","authors":"Wenhui Huang, Bin Bi, Qilan Huang, Haijing Wu, Xinghan Cheng, Li Pan","doi":"10.1165/rcmb.2025-0319OC","DOIUrl":"10.1165/rcmb.2025-0319OC","url":null,"abstract":"<p><strong>Background: </strong>Cisplatin resistance remains a major barrier to effective lung cancer treatment. This study explores the function of spliceosome associated factor 3 (SART3) in cisplatin resistance in non-small cell lung cancer (NSCLC).</p><p><strong>Methods: </strong>H1299 and Calu-3 cells were exposed to incremental doses of cisplatin to generate resistant cell lines. SART3 deletion and re-expression was induced in these resistant cell lines, followed by analysis of cell viability, proliferation, and DNA damage and repair markers. Metabolic analysis was performed in cells upon SART3 loss or re-expression. Palmitic acid (PA) and Etomoxir, a CPT1A inhibitor, and gain- and loss-of-function assays of CD36 were applied to analyze the involvement of β-oxidation pathway in SART3-mediated cisplatin resistance. The interacting proteins of SART3 were explored using immunoprecipitation/liquid chromatography-mass spectrometry assays, and their effects on CD36 transcription were analyzed with immunoprecipitation and luciferase assays.</p><p><strong>Results: </strong>SART3 was upregulated in cisplatin-resistant NSCLC cells. SART3 deletion sensitized cells to cisplatin, whereas re-expression restored resistance. Mechanistically, SART3 enhanced DNA repair mainly through the PARP pathway, and its deletion increased gH2AX levels and reduced BrdU incorporation. Metabolic analysis revealed that SART3-driven resistance relied on elevated fatty acid (FA) β-oxidation. Targeting FA metabolism with CPT1A inhibitors or CD36 antagonists, or blocking PARP activity, significantly reversed SART3-mediated resistance. Further, SART3 recruited FOXM1 to activate CD36 transcription by modulating H2b deubiquitination. In vivo, inhibition of the SART3-CD36-PARP axis suppressed tumor growth and restored cisplatin sensitivity in mice.</p><p><strong>Conclusion: </strong>This study suggests that SART3-driven metabolic reprogramming and DNA repair underpin cisplatin resistance.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"518-533"},"PeriodicalIF":5.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273653","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":"Lung CD14dimCD16high nonclassical monocytes are associated with systemic inflammation and cardiovascular disease risk in COPD.","authors":"Takuya Saito, Naoya Fujino, Shuichi Konno, Yoshinao Ono, Takuto Endo, Shuichiro Matsumoto, Mitsuhiro Yamada, Yoshinori Okada, Tracy Hussell, Hisatoshi Sugiura","doi":"10.1165/rcmb.2025-0119LE","DOIUrl":"10.1165/rcmb.2025-0119LE","url":null,"abstract":"","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"558-562"},"PeriodicalIF":5.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273640","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":"Hyperoxia and surfactant dysfunction in critical illness: insights and future therapeutic prospects.","authors":"Alastair Watson, Thomas Roe, Isis Terrington, Anthony D Postle, Daniel Martin, Michael P W Grocott, Ahilanandan Dushianthan","doi":"10.1165/rcmb.2025-0358TR","DOIUrl":"10.1165/rcmb.2025-0358TR","url":null,"abstract":"<p><p>Supplemental oxygen is an essential therapy during critical illness. However, patients with severe hypoxemic respiratory failure and/or acute respiratory distress syndrome often require high oxygen concentrations, exposing lungs to alveolar hyperoxia despite systemic hypoxemia, with consequent pulmonary oxygen toxicity. Pulmonary oxygen toxicity causes disruption of surfactant, which is essential for maintenance of alveolar functional anatomy, as well as efficient and effective gas exchange and immune regulation. This surfactant dysregulation can increase alveolar surface tension, causing alveolar collapse with atelectasis, resulting in poor lung compliance and impaired gas exchange. Hyperoxia-induced lung injury mechanisms may interact with mechanisms of harm associated with infections and mechanical ventilation. The intricate relationship between these different, interrelated stressors and altered surfactant metabolism and function is not yet delineated, particularly in humans. This review examines the current understanding of hyperoxia-induced surfactant dysregulation. We discuss potential mechanisms, including biochemical/compositional and functional changes to lipids and proteins including surfactant proteins A and D, epithelial atrophy, impaired surfactant synthesis/metabolism, redox imbalances, phospholipase A2, and altered macrophage clearance. Key areas for future research are outlined, emphasizing the need for clinically relevant human models that discriminate between the effects of oxygen therapy dose and duration, as well as other iatrogenic effects and underlying disease processes. We propose a roadmap to progress current knowledge and outline opportunities for well-designed human studies, novel surfactant preparations resistant to functional inhibition and breakdown, and technological developments, with the potential for leveraging these to identify innovative biomarkers, individualized therapeutic targets, and novel therapies in the future.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"427-444"},"PeriodicalIF":5.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079552","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":"Thymic stromal lymphopoietin promotes ozone-induced inflammation in the airway.","authors":"Hiroki Tashiro, Yuki Kurihara, Yuki Kuwahara, Yoshie Konomi, Masato Asaoka, Hiroki Kabata, Koichi Fukunaga, Ayako Takamori, Toshihiro Morisaki, Shinya Kimura, Naoko Sueoka-Aragane, Koichiro Takahashi","doi":"10.1165/rcmb.2025-0281OC","DOIUrl":"10.1165/rcmb.2025-0281OC","url":null,"abstract":"<p><strong>Rationale: </strong>Ozone is associated with induction of airway hyperresponsiveness (AHR) and neutrophilic airway inflammation which is the characteristic of type 2 low inflammatory phenotype. Recently, epithelial cell-derived cytokines such as thymic stromal lymphopoietin (TSLP) have been recognized as therapeutic targets for asthma with type 2 low inflammation, but the mechanisms remain unknown.</p><p><strong>Methods: </strong>BALB/c mice and TSLP receptor-deficient mice were exposed to ozone at 2 ppm for 3 hours. AHR, cell counts, and cytokine analyses of bronchoalveolar lavage fluid (BALF) were examined. Single-cell RNA sequencing was performed to explore targeted cell clusters and genes. Batf3-deficient mice were analyzed to assess the effects of conventional type 1 dendritic cells (cDC1s), and treatment with NP-G2-044 was given to evaluate the impact of Fscn1 on ozone-induced airway responses.</p><p><strong>Results: </strong>Ozone-exposed BALB/c mice showed greater AHR and neutrophils in BALF, with higher levels of TSLP in lungs than air-exposed BALB/c mice. Ozone-exposed TSLP receptor-deficient mice showed lower AHR and neutrophil counts in BALF than BALB/c mice. Single-cell RNA sequencing showed that DCs, especially cDC1s, were modified by ozone exposure and blockade of TSLP in terms of gene expressions including Fscn1. Ozone-exposed Batf3-deficient mice showed lower AHR and neutrophil counts in BALF, with depletion of cDC1s compared with C57BL/6J mice. Expression of Fscn1 was greater in bone marrow-derived cDC1s stimulated by TSLP, and ozone-exposed BALB/c mice treated with NP-G2-044 showed lower neutrophils in BALF than BALB/c mice treated with placebo.</p><p><strong>Conclusions: </strong>cDC1 derived Fscn1 was a potential target for ozone-induced neutrophilic airway inflammation via TSLP.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"497-517"},"PeriodicalIF":5.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145197916","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":"SERPINB10 promotes neutrophilic airway inflammation in asthma.","authors":"Weiqiang Kong, Chunli Huang, Lu Zhao, Gongqi Chen, Wei Gu, Huiru Jie, Zhen Wang, Tiantian Xiong, Lingling Yi, Yuchen Feng, Guohua Zhen","doi":"10.1165/rcmb.2024-0580OC","DOIUrl":"10.1165/rcmb.2024-0580OC","url":null,"abstract":"<p><strong>Rationale: </strong>A subset of severe asthma is characterized by neutrophilic airway inflammation in which epithelial activation of the NLRP3 inflammasome pathway is implicated. SERPINB10 is linked to neutrophil activation in inflammatory diseases.</p><p><strong>Objectives: </strong>To investigate the role of SERPINB10 in airway neutrophilia in asthma.</p><p><strong>Methods: </strong>We sensitized mice with house dust mite (HDM) and challenged them with HDM and poly(I: C), a viral double-stranded RNA analog. Airway inflammation and the expression of inflammatory cytokines in mouse lungs were analyzed. Mechanistic experiments were performed in HBE cells by RNA sequencing, western blotting, and immunofluorescence staining. The expression of SERPINB10, NLRP3, IL-1β, and IL-6 were determined in human bronchial brushings.</p><p><strong>Measurements and main results: </strong>Serpinb10 -/- mice exhibited reduced neutrophil counts in bronchoalveolar lavage cells and alleviated inflammatory cell infiltration around airways. Il-1β and Il-6 expression was decreased in lung tissues from Serpinb10-/- mice. In cultured HBE cells, SERPINB10 knockdown decreased IκBα phosphorylation and suppressed poly(I: C)-induced IL-1β and IL-6 expression. Moreover, the expression of NLRP3 and pro-IL-1β in lung tissues of Serpinb10-/- mice was decreased. Conversely, SERPINB10 overexpression enhanced IL-1β and IL-6 expression in HBE cells, which was blocked by either an IκBα phosphorylation inhibitor or an NLRP3 inhibitor. Of note, SERPINB10 expression in bronchial brushings from non-eosinophilic asthma patients was enhanced and significantly correlated with the severity of airflow limitation, and the expression of NLRP3, IL-1β, and IL-6.</p><p><strong>Conclusions: </strong>SERPINB10 promotes IL-1β and IL-6 expression by upregulating NF-κB and NLRP3 signaling in airway epithelial cells, thereby driving neutrophilic airway inflammation in asthma.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"547-557"},"PeriodicalIF":5.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273661","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":"Enhancing the antifibrotic potential of the endothelium: lipid nanoparticles to the rescue.","authors":"Patricia L Brazee, Rachel S Knipe","doi":"10.1165/rcmb.2025-0563ED","DOIUrl":"10.1165/rcmb.2025-0563ED","url":null,"abstract":"","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"419-420"},"PeriodicalIF":5.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145297897","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":"CCL18 with an attitude: unlocking the role of macrophage CCL18 in checkpoint inhibitor pneumonitis.","authors":"Nathanial J Tolman, William Bain","doi":"10.1165/rcmb.2025-0576ED","DOIUrl":"10.1165/rcmb.2025-0576ED","url":null,"abstract":"","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"421-422"},"PeriodicalIF":5.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145385826","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":"FABP4&5: another brick in the lipid road of pulmonary arterial hypertension?","authors":"Sophie Nadaud","doi":"10.1165/rcmb.2025-0438ED","DOIUrl":"10.1165/rcmb.2025-0438ED","url":null,"abstract":"","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"423-424"},"PeriodicalIF":5.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145297923","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}