American journal of physiology. Lung cellular and molecular physiology最新文献

{"title":"Take a chance on me: apply for the next round of Editorial Fellows.","authors":"Larissa A Shimoda, Cristina M Alvira, Julie A Bastarache, Rodney D Britt, Rachel S Knipe, Wolfgang M Kuebler, Thiago S Moreira, Eric P Schmidt","doi":"10.1152/ajplung.00254.2026","DOIUrl":"10.1152/ajplung.00254.2026","url":null,"abstract":"","PeriodicalId":7593,"journal":{"name":"American journal of physiology. Lung cellular and molecular physiology","volume":" ","pages":"L341-L343"},"PeriodicalIF":3.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13527820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148496945","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":"Opening the black box: reflections from the AJP-Lung early career editorial fellows.","authors":"Stefan Hadzic, Simon J Cleary, Daniel Colon Hidalgo, Jana Grune, Kadija Hersi, Corrine R Kliment, Elena Lopez-Rodriguez, Jamie E Meegan, Samuel G Rayner, Kent A Willis, Alicia N Rizzo","doi":"10.1152/ajplung.00251.2026","DOIUrl":"10.1152/ajplung.00251.2026","url":null,"abstract":"","PeriodicalId":7593,"journal":{"name":"American journal of physiology. Lung cellular and molecular physiology","volume":" ","pages":"L338-L340"},"PeriodicalIF":3.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148468399","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":"Central cholinergic modulation of the cough reflex: suppressive effects of donepezil in rabbits.","authors":"Claudia Vitale, Elenia Cinelli, Alessandra Sorano, Giulia Fabietti, Federico Lavorini, Donatella Mutolo","doi":"10.1152/ajplung.00136.2026","DOIUrl":"10.1152/ajplung.00136.2026","url":null,"abstract":"<p><p>Cough is a purposeful airway-defensive reflex, but in chronic cough it no longer provides a clear physiological benefit and markedly impairs patient's quality of life. Currently available antitussive drugs have limited efficacy and may cause severe side effects. Thus, further research is needed to find reliable treatments. It has been shown that acetylcholine (ACh) downregulates cough via muscarinic ACh receptors (mAChRs) in the rabbit caudal portion of the nucleus tractus solitarii (cNTS), with a major involvement of the M₄ receptor subtype. The identification of cholinergic agents modulating Ach-depressant effects on coughing could be of considerable interest for the development of novel therapeutic strategies. Here, we tested the hypothesis that increasing synaptic ACh levels by inhibiting acetylcholinesterase activity may downregulate the cough reflex. In anesthetized, spontaneously breathing rabbits, we investigated the effect of donepezil, a brain-penetrant, potent, and selective acetylcholinesterase inhibitor, on the modulation of the cough reflex induced by mechanical and chemical stimulation of the tracheobronchial tree and on the sneeze reflex. Efferent respiratory and electromyographic activities were recorded from phrenic nerves and abdominal muscles, respectively. Donepezil, either systemically administered (5 mg/kg sc) or bilaterally microinjected (5 mM; 30-50 nL) into the cNTS, induced strong depressant effects up to the complete abolition of the mechanically induced cough, without affecting sneezing. Donepezil also decreased expiratory activity even to complete suppression, whereas transient increases in respiratory frequency were observed only after local application. These findings support further investigation of donepezil and related centrally acting cholinergic agents as candidate antitussive therapies.<b>NEW & NOTEWORTHY</b> Acetylcholine (ACh) downregulates cough in the rabbit caudal portion of the nucleus tractus solitarii (NTS). We show that the acetylcholinesterase inhibitor donepezil markedly suppresses the cough reflex at this site. These findings identify central cholinergic modulation as a promising pathway for the development of novel antitussive strategies.</p>","PeriodicalId":7593,"journal":{"name":"American journal of physiology. Lung cellular and molecular physiology","volume":" ","pages":"L277-L288"},"PeriodicalIF":3.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148648169","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":"Testosterone alleviates inflammation but increases the methacholine response in male mice with allergic lung inflammation.","authors":"Cyndi Henry, Magali Boucher, Andrés Rojas-Ruiz, Louane Camillari, Louis Gélinas, Marie-Josée Beaulieu, David Marsolais, Vincent Joseph, Ynuk Bossé","doi":"10.1152/ajplung.00165.2026","DOIUrl":"10.1152/ajplung.00165.2026","url":null,"abstract":"<p><p>Testosterone seems protective against asthma, but the underlying mechanisms are uncertain. Although several of its anti-inflammatory properties have been described, its effect on respiratory mechanics and the methacholine response are incompletely understood. Herein, the effect of testosterone was investigated on several features of experimental asthma with a special focus on respiratory mechanics and the methacholine response. Systemic testosterone was first altered to subphysiological, physiological, or supraphysiological levels in male BALB/c mice through orchiectomy and testosterone supplementation. Testosterone (0.25 mg/day/30 g of body weight) was delivered continuously during 20 days using an implanted pump. At <i>day 10</i>, each group was exposed intranasally to either saline or house dust mite (HDM) once daily for 10 consecutive days to induce allergic lung inflammation. The day after the last exposure, respiratory mechanics were measured at baseline and in response to nebulized methacholine. Bronchoalveolar lavages (BAL) and lung tissues were also collected to quantify inflammation. Baseline respiratory mechanics were altered in mice with subphysiological levels of testosterone, with signs of small airway narrowing heterogeneity and closure. Testosterone drastically inhibited the HDM-induced inflammation. Yet, testosterone also increased the methacholine response, which occurred to the same extent in mice with and without experimental asthma. It is concluded that testosterone improves baseline respiratory mechanics and, although it increases the methacholine response, it does not synergistically amplify hyperresponsiveness in a context of experimental asthma, probably because it concurrently decreases inflammation.<b>NEW & NOTEWORTHY</b> Male mice with three distinct levels of testosterone were evaluated in a common mouse model of asthma induced by house dust mite exposures. Although testosterone decreased allergic lung inflammation, it also increased the response to nebulized methacholine. This mismatch between inflammation and the methacholine response informed about how different features of experimental asthma can be swayed in different directions by a single molecular mediator.</p>","PeriodicalId":7593,"journal":{"name":"American journal of physiology. Lung cellular and molecular physiology","volume":" ","pages":"L265-L276"},"PeriodicalIF":3.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148672941","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":"The role of endothelial <i>HIF-1<b>α</b></i> in vascular and alveolar development in a neonatal murine model of bronchopulmonary dysplasia.","authors":"Han-Pi Chang, Abiud Cantu, Manuel Eliezer Cantu Gutierrez, Krithika Lingappan","doi":"10.1152/ajplung.00073.2026","DOIUrl":"10.1152/ajplung.00073.2026","url":null,"abstract":"<p><p>Bronchopulmonary dysplasia (BPD), a lung disease associated with preterm birth, is characterized by arrested alveolarization and impaired pulmonary vascular growth. Exposure to early life hyperoxia is a disease-contributing factor, and endothelial determinants of injury versus repair remain incompletely defined. We hypothesized that endothelial-specific loss of <i>Hif-1α</i> during the saccular stage of development would adversely impact lung development and augment injury after hyperoxia exposure. Tamoxifen-inducible endothelial-specific <i>Hif-1α</i> knockout and <i>Hif-1α</i>^fl/fl littermates were exposed to room air or 95% O₂ from <i>postnatal day</i> (PND) <i>1</i>-<i>5</i>, and lungs were analyzed at PND7 and PND21 for morphometry, vascular density, and lung endothelial transcriptomic response. Endothelial <i>Hif-1α</i> deletion had no impact on baseline alveolarization but reduced vascular density under normoxia and significantly worsened hyperoxia-induced alveolar simplification, septal thickening, and vascular rarefaction. Hyperoxia increased endothelial proliferation in both genotypes after 48 h of recovery in normoxia. Bulk RNA sequencing of the lung endothelial cells revealed a shared hyperoxia injury program (e.g., <i>Inhba</i>, <i>Serpine1</i> induction; <i>Esm1</i>, <i>Gpihbp1</i>, <i>Car2</i> suppression). The transcriptomic response in <i>HIF1α</i>^ECKO endothelial cells was significantly muted compared with wild-type endothelial cells, lacking induction of <i>Hmox1</i>, <i>Prdx6</i>, and <i>Anxa1</i>. <i>Hif-1α</i>-deficient endothelial cells upregulated <i>Col18a1</i> and <i>Ackr3</i> and showed enrichment of TNF-NF-κB, TGF-β, and cell-cycle checkpoint pathways, consistent with maladaptive remodeling. Cross-referencing with human single-cell BPD data demonstrated that genes identified in the murine hyperoxia model exhibit conserved but heterogeneous endothelial expression patterns across BPD disease states. These findings identify endothelial <i>Hif-1α</i> as a central determinant of recovery after neonatal hyperoxia exposure.<b>NEW & NOTEWORTHY</b> This study identifies endothelial hypoxia-inducible factor-1α (HIF-1α) as a critical determinant of neonatal lung response to hyperoxia. Using an inducible endothelial-specific <i>Hif-1α</i> knockout model, we demonstrate that loss of endothelial <i>Hif-1α</i> exacerbates hyperoxia-induced impairments in pulmonary vascular development and alveolarization, key pathological features of bronchopulmonary dysplasia.</p>","PeriodicalId":7593,"journal":{"name":"American journal of physiology. Lung cellular and molecular physiology","volume":" ","pages":"L312-L326"},"PeriodicalIF":3.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148597691","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":"Endothelial-derived extracellular vesicles impair human pulmonary microvascular cell function in an in vitro model of sepsis-induced acute lung injury.","authors":"Maya Cohen, Liana Haigis, Rebecca C Blum, Allyson Sherman-Roe, Mandy Pereira, Havovi Chichger, Corey E Ventetuolo, Olin D Liang, Elizabeth O Harrington","doi":"10.1152/ajplung.00287.2025","DOIUrl":"10.1152/ajplung.00287.2025","url":null,"abstract":"<p><p>Acute respiratory distress syndrome (ARDS) remains a critical condition associated with high morbidity and mortality, particularly when triggered by sepsis. Endothelial dysfunction is a central hallmark of ARDS pathology, but the precise mechanisms underlying pulmonary microvascular dysfunction remain poorly understood. Extracellular vesicles (EVs) have emerged as crucial mediators of cell-cell communication during inflammation; however, their role in endothelial dysfunction in ARDS is less clearly defined. We utilized a human pulmonary microvascular endothelial cell (HPMEC)-based model of sepsis-induced acute lung injury to investigate whether inflammatory EVs (iEVs), derived from endothelial cells treated with bacterial lipopolysaccharide (LPS), impair naïve HPMEC function. EVs were characterized by nanoparticle tracking analysis, transmission electron microscopy, and immunofluorescence, confirming purity and uptake. iEV exposure significantly reduced barrier integrity by electric cell-substrate impedance sensing (ECIS) and increased cell migration; effects partially reversed by the toll-like receptor 4 (TLR4) inhibitor TAK-242. Adhesion and tube formation were unaffected. Pretreatment of donor HPMECs with the neutral sphingomyelinase inhibitor GW4869 attenuated the barrier-disrupting capacity of the resulting iEVs, implicating ceramide-dependent EV biogenesis in generating pathogenic cargo. Trypan Blue staining confirmed that these effects reflect altered signaling rather than cell death. iEV exposure upregulated TLR4, MyD88, interleukin-6 (IL-6), intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), E-selectin, and <i>Jag1</i> mRNA, with TAK-242 attenuating IL-6 and ICAM-1 induction. Our results highlight endothelial-derived EVs and TLR4-dependent pathways as amplifiers of pulmonary vascular injury in sepsis-induced ARDS, identifying EV biogenesis and EV-mediated signaling as novel therapeutic targets.<b>NEW & NOTEWORTHY</b> EVs released from LPS-stimulated human pulmonary microvascular endothelial cells compromise barrier integrity and enhance migration via TLR4-mediated signaling. Inhibition of ceramide-dependent EV biogenesis with GW4869 attenuated barrier dysfunction, implicating specific EV subpopulations as pathogenic mediators. EV-TLR4 activation upregulates MyD88 and IL-6, suggesting an autocrine loop amplifying vascular injury in sepsis-induced ARDS, and identifying EV biogenesis and EV-mediated TLR4 signaling as novel therapeutic targets.</p>","PeriodicalId":7593,"journal":{"name":"American journal of physiology. Lung cellular and molecular physiology","volume":" ","pages":"L252-L264"},"PeriodicalIF":3.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13463783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148468385","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":"Mechanical and chemical power and mortality in acute respiratory distress syndrome: an exploratory analysis of six patient cohorts.","authors":"Thijs A Lilien, Lieuwe D J Bos, Lukas Martin Mueller-Wirtz, Pien Swart, Siebe G Blok, Luciano Cesar Pontes Azevedo, Giacomo Bellani, Michela Botta, Elisa Estenssoro, Eddy Fan, Juliana Carvalho Ferreira, Hendrik Helmerhorst, John G Laffey, Ignacio Martin-Loeches, Ana Motos, Tai Pham, Óscar Peñuelas, Antonio Pesenti, Ary Serpa Neto, Emanuele Rezoagli, Antoni Torres, Anissa M Tsonas, Frederique Paulus, Marcus J Schultz, David M P van Meenen, Reinout A Bem","doi":"10.1152/ajplung.00070.2026","DOIUrl":"10.1152/ajplung.00070.2026","url":null,"abstract":"<p><p>Invasive ventilation with oxygen supplementation may inadvertently cause ventilator- and hyperoxia-induced lung injury, respectively, but their balance is fairly unaddressed. The concept of mechanical power summarizes factors of ventilation intensity associated with development of ventilator-induced lung injury. More recently, we introduced the theoretical framework for chemical power to estimate risk of hyperoxia-induced injury and allow for integration of both mechanical and chemical energy transfer per unit time. In the current study, we explored the associations of mechanical and chemical power with outcomes in mechanically ventilated patients with acute respiratory distress syndrome. In this secondary analysis of six pooled cohort studies, patients with acute respiratory distress syndrome per Berlin criteria and available data to calculate chemical and mechanical power on <i>days 1</i> and <i>2</i> of invasive ventilation were selected. The primary outcome was all-cause 60-day mortality. A total of 2,117 patients were included in the main analysis. Higher chemical power levels were associated with increased 60-day mortality (<i>P</i> < 0.001), regardless of the mechanical power levels. Increasing mechanical power levels combined with decreasing chemical power levels was associated with a better outcome than vice versa (<i>P</i> < 0.001). There was no interaction between both powers. In this pooled cohort study of acute respiratory distress syndrome patients receiving invasive ventilation, higher chemical power levels were associated with a higher rate of mortality, independent of mechanical power levels. These results support further experimental validation of the concept of chemical power and exploration of its balance with mechanical power to predict outcome of lung injury.<b>NEW & NOTEWORTHY</b> This observational study of a combined cohort of patients with acute respiratory distress syndrome assessed the association of the novel concept of chemical power, a surrogate marker of oxygen exposure intensity, with mortality and its relative weight in this association when compared with mechanical power. Chemical power and mechanical power were independently associated with mortality. An interaction between these powers was not observed. Future experimental studies should aim to validate and optimize this novel concept.</p>","PeriodicalId":7593,"journal":{"name":"American journal of physiology. Lung cellular and molecular physiology","volume":" ","pages":"L289-L298"},"PeriodicalIF":3.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148683063","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":"Molecular mechanisms underlying FCCP-induced mitophagy in human airway smooth muscle cells.","authors":"Sanjana Mahadev Bhat, Oscar A Ramirez Ramirez, Gary C Sieck","doi":"10.1152/ajplung.00050.2026","DOIUrl":"10.1152/ajplung.00050.2026","url":null,"abstract":"<p><p>Mitophagy is a selective autophagic process that eliminates damaged mitochondria, which is essential for mitochondrial quality control and cellular homeostasis. The most extensively characterized mitophagy pathway involves PTEN-induced kinase 1 (PINK1) and E3 ubiquitin ligase Parkin. Upon mitochondrial depolarization, PINK1 stabilizes on the outer mitochondrial membrane (OMM), where it recruits and phosphorylates Parkin at serine 65 (pParkin^S65), activating its E3 ligase activity. Active pParkin^S65 initiates the ubiquitination (Ub) of OMM proteins, resulting in the engulfment and lysosomal degradation of damaged (depolarized) mitochondria. Carbonyl cyanide-<i>p</i>-trifluoromethoxyphenylhydrazone (FCCP), a mitochondrial uncoupler, is widely used to experimentally induce mitochondrial depolarization and initiate PINK1-Parkin-dependent mitophagy; however, mitophagic responses to FCCP vary across cell types. In the present study, we hypothesized that, in human airway smooth muscle (hASM) cells, FCCP-induced mitochondrial depolarization activates the PINK1-Parkin-mediated mitophagy pathway, culminating in the clearance of damaged mitochondria. We observed that exposing hASM cells to 1 µM FCCP for 6 h induced mitochondrial depolarization and a decrease in the volume of intact mitochondria. This mitochondrial depolarization triggered the accumulation of PINK1 in the mitochondria, which mediated phosphorylation of pParkin^S65 and pUb^S65. Confocal imaging of labeled mitochondria and lysosomes demonstrated increased colocalization of mitochondria with lysosomes, and mitophagic flux was confirmed using a pH-sensitive mitochondrial reporter mKeima. Collectively, these findings demonstrate that FCCP robustly activates the canonical PINK1-Parkin mitophagy pathway in hASM cells, providing mechanistic insight into mitochondrial quality control, with potential relevance to airway diseases characterized by mitochondrial dysfunction and altered hASM function.<b>NEW & NOTEWORTHY</b> The study establishes the presence of a robust mitophagic response to acute mitochondrial depolarization in hASM cells mediated through the canonical PINK1-Parkin pathway. By integrating quantitative mitochondrial labeling and biochemical analyses, we demonstrate increased mitochondrial damage and remodeling, accompanied by mitochondrial PINK1 accumulation and Parkin activation, resulting in ubiquitin-dependent signaling and lysosomal engulfment. These findings identify mitophagy as a critical adaptive mechanism for maintaining mitochondrial quality control in airway smooth muscle cells during metabolic stress.</p>","PeriodicalId":7593,"journal":{"name":"American journal of physiology. Lung cellular and molecular physiology","volume":" ","pages":"L233-L251"},"PeriodicalIF":3.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13487762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148576716","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":"Conversations in collagen: multicellular cross talk shapes the fibrotic niche in pulmonary fibrosis.","authors":"Rebecca J Salamon, Shally Saini","doi":"10.1152/ajplung.00426.2025","DOIUrl":"10.1152/ajplung.00426.2025","url":null,"abstract":"<p><p>Pulmonary fibrosis is often framed as a problem of excess collagen causing stiffening of the lung, but that framing misses the more dynamic reality: fibrosis is built through ongoing conversations between fibroblasts, neighboring cells, and extracellular matrix (ECM) that interpret and reinforce injury signals. Over the last 3 years, single-cell, spatial, and multiomics tools, paired with lineage tracing and functional models, have revealed distinct fibroblast states, trajectories, and spatial niches with increasing resolution. Here, we summarize emerging principles from this sharpened point of view. First, lung fibroblasts are not a single \"myofibroblast\" entity; rather, they include a spectrum of states, ranging from resident niche-supporting lipofibroblasts, to transitional and inflammatory intermediate states, to CTHRC1⁺ pathological states. These transitions are not strictly linear, potentially reversible, and are context-dependent. Second, fibroblast state transitions are shaped by signals from injury-associated epithelial and immune cell populations within multicellular niches. Third, the ECM is not a passive scar; rather, it is an active signaling hub whose composition, cross linking, and stiffness engage mechanotransduction pathways that reinforce and, in chronic fibrosis, may lock in pathological fibroblast states. These insights motivate more precise therapeutic strategies-targeting fibroblast state-specific vulnerabilities, disrupting the fibrotic niche, and correcting dysregulated mechanosensing-and raise open questions about fibroblast state reversibility and niche plasticity that will shape next-generation approaches.</p>","PeriodicalId":7593,"journal":{"name":"American journal of physiology. Lung cellular and molecular physiology","volume":" ","pages":"L327-L337"},"PeriodicalIF":3.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148652982","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":"The ferroptosis inhibitor NUPR1 coordinates the mitochondrial response to oxidative stress and cell metabolism during COPD pathogenesis in the lung.","authors":"Jessica Nouws, Saul S Siller, Tao Yang, So-Jin Kim, Sang-Hun Kim, Patricia Santofimia-Castaño, Juan L Iovanna, Erica L Herzog, John E McDonough, Maor Sauler","doi":"10.1152/ajplung.00098.2026","DOIUrl":"10.1152/ajplung.00098.2026","url":null,"abstract":"<p><p>Chronic obstructive pulmonary disease (COPD) is characterized by chronic injury and oxidative stress leading to progressive lung tissue destruction. Emerging evidence suggests that regulated cell death pathways, particularly ferroptosis, contribute to COPD pathology. We previously identified decreased expression of the stress response protein and known ferroptosis inhibitor nuclear protein 1 (NUPR1) in alveolar type 2 cells from COPD patients. Here, we demonstrate that NUPR1 inhibition exacerbates iron accumulation, enhances lipid peroxidation, impairs mitochondrial function, disrupts cellular metabolism, and increases oxidative stress in lung epithelial cells. Furthermore, <i>Nupr1-/-</i> mice exhibit mitochondrial abnormalities, increased oxidative damage, and lung tissue changes consistent with emphysema. Collectively, our findings establish NUPR1 as a critical regulator of ferroptosis, stress responses, mitochondrial integrity, as well as metabolic balance in the lung and suggest reduced NUPR1 contributes to COPD pathogenesis.</p>","PeriodicalId":7593,"journal":{"name":"American journal of physiology. Lung cellular and molecular physiology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148786723","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}