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

{"title":"Early dysanapsis in experimental bronchopulmonary dysplasia: implications for lifelong lung disease.","authors":"Elizabeth A McGinn, Alexander Sosa, Mary Corrigan, Gregory Seedorf, Jennifer Mecklenburg, Livia A Veress, Steven H Abman, Bradford J Smith, Erica W Mandell","doi":"10.1152/ajplung.00152.2026","DOIUrl":"10.1152/ajplung.00152.2026","url":null,"abstract":"<p><p>Disruptions during perinatal fetal lung development can lead to postnatal chronic lung diseases such as bronchopulmonary dysplasia (BPD). Along with decreased alveolar and pulmonary vascular growth, abnormal airway growth occurs in BPD. Previous studies in rats have shown that antenatal endotoxin (AN-ETX) mimicking maternal chorioamnionitis causes dysanapsis during the neonatal period. Whether dysanaptic growth alters long-term lung function remains unknown. We hypothesized that antenatal endotoxin causes persistent differences between airway and distal lung growth with age in experimental BPD. Sprague-Dawley rats were exposed to AN-ETX at <i>embryonic day 20</i> (E20) by intraamniotic injection and delivered on E22, analogous to human preterm 26-28 wk gestation. Pups raised via naive foster dams were evaluated for BPD-associated parameters on postnatal <i>days 14</i> (D14) and <i>28</i> (D28), akin to infancy and childhood human lung development. Lung histologic morphometry, lung mechanics testing, and airway and pulmonary vasculature microcomputed tomography (µCT) evaluations were performed to assess growth at D14 and D28. AN-ETX-exposed rats demonstrated persistent somatic growth failure, decreased alveolarization, decreased vascularization, right ventricular hypertrophy, and impaired lung mechanics at both D14 and D28. AN-ETX exposure decreased large airway size at D14, but also medium airway diameters by D28. AN-ETX exposure caused early airflow obstruction at D14 [decreased forced expiratory volume over 0.1 s to forced vital capacity (FEV_0.1/FVC) ratio], which worsened by D28 (decreased FEV_0.1 and FEV_0.1/FVC ratio). Adverse antenatal stress alone is sufficient to cause sustained abnormalities of lung development beyond the neonatal period. Early dysanapsis may predispose to structural obstructive disease and impair lung function over the lifespan.<b>NEW & NOTEWORTHY</b> Disruptions during perinatal lung development can lead to chronic lung diseases such as bronchopulmonary dysplasia (BPD). Rats exposed to a single intraamniotic endotoxin injection were evaluated for BPD-associated parameters of lung structure and function on postnatal <i>days 14</i> and <i>28</i>, akin to human infancy and childhood. Endotoxin-exposed rats demonstrated persistent impairments in lung development and function. This is the first preclinical study to suggest that early dysanaptic growth may predispose to lifelong impaired lung function.</p>","PeriodicalId":7593,"journal":{"name":"American journal of physiology. Lung cellular and molecular physiology","volume":" ","pages":"L165-L177"},"PeriodicalIF":3.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13420720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148337387","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":"Impaired mucociliary clearance in bronchiectasis: the result of a differentiation-delayed airway epithelium?","authors":"Andrew T Reid, Punnam Chander Veerati, Kristy S Nichol, Michael Schuliga, Jane M Read, Adam M Collison, Peter A B Wark, Felicia Ton, Christopher L Grainge","doi":"10.1152/ajplung.00321.2025","DOIUrl":"10.1152/ajplung.00321.2025","url":null,"abstract":"<p><p>Impaired mucociliary clearance (MCC) is a potential targetable feature of bronchiectasis; however, it is difficult to model outside of the patient, and thus, there remains little mechanistic evidence to suggest what drives it. To unravel the complexities associated with assessing mucociliary clearance we have established a four-parameter assessment, the Newcastle Cilia and Mucus (NewCAM) score, which quantifies active ciliated area, cilia beat frequency, apical particle velocity, and mucus viscosity in vitro. In addition, single-cell RNA (scRNA) sequencing was used to assess the breakdown of epithelial cell types within this model. Bronchial epithelial cells from bronchiectasis donors, cultured for 28 days at the air-liquid interface (ALI), exhibited lower active ciliated area (<i>P</i> < 0.05) and apical particle velocity (<i>P</i> < 0.05) compared with healthy donor cells using NewCAM. scRNA analysis indicated a modest increase in immature basal cell-types in bronchiectasis donor cultures, at the expense of terminally differentiated cell-types such as ciliated and secretory cells during differentiation. Taken together, these results suggest that bronchial epithelial cells from bronchiectasis donors are temporally delayed in their differentiation and fail to meet levels of MCC observed in their healthy counterparts under equivalent growth conditions over the same timeframe.<b>NEW & NOTEWORTHY</b> In vitro differentiated cultures of primary bronchial epithelial cells taken from bronchiectasis donors exhibited fewer motile ciliated bundles compared with healthy donors cultured for the same period. Using the newly designed the Newcastle Cilia and Mucus (NewCAM) scoring system, this reduction translates to a reduction in effective mucociliary clearance in vitro. Single-cell RNA data from these cultures indicated more basal cell types and fewer terminally differentiated epithelial cells from bronchiectasis donors, suggesting delayed differentiation in bronchiectasis.</p>","PeriodicalId":7593,"journal":{"name":"American journal of physiology. Lung cellular and molecular physiology","volume":" ","pages":"L1-L15"},"PeriodicalIF":3.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147985955","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":"Advances in human lung disease models: stem cell-based platforms for modeling airway and alveolar disease.","authors":"Daniel J Wallman, Sinem Koc-Gunel, Robert E Hynds, Amy L Ryan, Ruth Olmer","doi":"10.1152/ajplung.00092.2026","DOIUrl":"10.1152/ajplung.00092.2026","url":null,"abstract":"<p><p>This mini-review, inspired by the 20th Anniversary Stem Cells, Cell Therapies and Bioengineering in Lung Biology and Diseases conference, summarizes two decades of advances in human-specific lung disease modeling. We discuss endogenous stem cell-based platforms for both distal alveolar and proximal airway epithelia, including primary alveolar type II cells, bronchial and nasal epithelial cultures established as organoids, air-liquid interface cultures, and ex vivo preparations. Advances in iPSC-derived basal and alveolar epithelial cells, humanized graft models, and high-throughput therapeutic screening are highlighted. Collectively, these in vitro and in vivo models are transforming the study of lung development, injury, and repair, while accelerating drug discovery and regenerative medicine strategies. Finally, we emphasize the critical need for integrating immune components into organotypic cultures and for establishing rigorous validation and benchmarking standards to maximize translational relevance.</p>","PeriodicalId":7593,"journal":{"name":"American journal of physiology. Lung cellular and molecular physiology","volume":" ","pages":"L48-L56"},"PeriodicalIF":3.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148136669","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":"Inhaled pattern recognition receptor agonists promote inducible epithelial resistance against murine betacoronavirus disease.","authors":"Michael K Longmire, Jezreel Pantaleón García, Raquel Alonso Becerra, Valerie B Oren, Oanh N Hoang, Jania Foncerrada Lizaola, Scott E Evans","doi":"10.1152/ajplung.00226.2025","DOIUrl":"10.1152/ajplung.00226.2025","url":null,"abstract":"<p><p>Coronaviruses can cause serious disease in humans and animals. They are often difficult to study due to the variability of the disease as well as safety concerns related to biosafety requirements. Here, we use a biological safety level (BSL) 2-compatible murine betacoronavirus (MHV-A59), which infects multiple organs, to study the respiratory phase of disease and subsequent systemic dissemination. We asked whether inducible epithelial resistance, activated by the combination of pattern recognition receptor agonists Pam2CSK4 (Pam2), synthetic diacylated lipopeptide, + oligodeoxynucleotide (ODN) M362, can limit both pulmonary infection and systemic spread of disease. Prophylactic exposure with Pam2 + ODN improves survival and reduces extrapulmonary viral burden, including in the liver, consistent with limited systemic spread. Stopping the infection at the level of the lungs is associated with improved physiological outcomes and increased protection for the mice. We further characterize the response of the epithelial cells to infection and treatment and demonstrate modulation of epithelial gene expression, including attenuation of virus-induced responses, to better understand the mechanisms of protection and how these responses may be leveraged against future infectious agents.<b>NEW & NOTEWORTHY</b> This study establishes a BSL 2-compatible murine betacoronavirus model to investigate respiratory and systemic disease. We show that inducible epithelial resistance via Pam2 + ODN improves survival, preserves lung function, and reduces extrapulmonary viral burden. Mechanistically, Pam2 + ODN reprograms lung epithelial gene expression, reversing virus-induced transcriptional responses. These findings support epithelial-targeted, pathogen-agnostic strategies to limit both pulmonary and systemic consequences of respiratory viral infection.</p>","PeriodicalId":7593,"journal":{"name":"American journal of physiology. Lung cellular and molecular physiology","volume":" ","pages":"L70-L78"},"PeriodicalIF":3.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13334886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148203783","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 modulators: a new class of antimicrobials in lung infection?","authors":"Lasti Erfinanda, Wolfgang M Kuebler","doi":"10.1152/ajplung.00099.2026","DOIUrl":"10.1152/ajplung.00099.2026","url":null,"abstract":"","PeriodicalId":7593,"journal":{"name":"American journal of physiology. Lung cellular and molecular physiology","volume":" ","pages":"L89-L91"},"PeriodicalIF":3.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148203780","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":"Macrophage in the crosshairs: chemical inhalation and lung immune defense.","authors":"Shama Ahmad, Aftab Ahmad","doi":"10.1152/ajplung.00008.2026","DOIUrl":"10.1152/ajplung.00008.2026","url":null,"abstract":"<p><p>Pulmonary macrophages are central regulators of lung injury and repair following acute inhalation of toxic chemicals. Strategically positioned within the airspaces and lung parenchyma, resident macrophage populations act as first responders that sense epithelial and endothelial injury, initiate sterile inflammatory responses, and coordinate immune cell recruitment, thereby influencing whether injury resolves or progresses to chronic inflammation and fibrosis. Recent advances have revealed substantial heterogeneity and plasticity among lung macrophages shaped by developmental origin, anatomical niche, and local microenvironmental cues. Alveolar and interstitial macrophages engage in extensive bidirectional cross talk with epithelial and endothelial cells through cytokines, growth factors, and extracellular vesicles that collectively maintain pulmonary homeostasis and regulate responses to injury. In experimental models of vesicant, particulate, volatile organic compounds, microbial toxins, and toxic gas exposure, pulmonary macrophages undergo profound transcriptional, metabolic, and functional reprogramming. Early depletion of resident alveolar macrophages coupled with disproportionate recruitment of monocyte-derived macrophages has emerged as a conserved pathogenic feature of severe chemical-induced lung injury. This review summarizes current understanding of pulmonary macrophage ontogeny, functional specialization, and macrophage-epithelial cross talk during acute chemical inhalation injury, and discusses emerging therapeutic strategies aimed at modulating macrophage responses to restore pulmonary homeostasis. Collectively, these insights position pulmonary macrophages as critical gatekeepers of lung injury and repair and as promising targets for intervention in chemical-induced lung disease.</p>","PeriodicalId":7593,"journal":{"name":"American journal of physiology. Lung cellular and molecular physiology","volume":" ","pages":"L105-L117"},"PeriodicalIF":3.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148238452","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":"Piecing together the alveolar-capillary unit: arterial-venous capillary polarization.","authors":"Susan M Majka, Terren K Niethamer, Nunzia Caporarello, Hannah F Thorndyke, Geremy Clair, James D West, Harry Karmouty-Quintana, Cristina M Alvira","doi":"10.1152/ajplung.00101.2026","DOIUrl":"10.1152/ajplung.00101.2026","url":null,"abstract":"<p><p>Pulmonary capillary endothelial cells (ECs) form a highly specialized vascular interface that sustains gas exchange and organismal survival across species. Recent advances in single-cell transcriptomics and lineage tracing have revealed substantial heterogeneity within the pulmonary endothelium, redefining traditional views of capillary structure and function. In the adult lung, two major capillary populations, general capillary ECs (CAP1) and aerocyte capillary ECs (CAP2), have been identified, with CAP1 cells increasingly recognized as a heterogeneous and functionally diverse compartment that includes EC progenitors and reparative subpopulations. Emerging datasets further demonstrate arterial-venous polarization within the capillary bed and reveal gradients of gene expression that extend from macrovascular arteries and veins into the alveolar microvasculature. Within this polarized CAP1 landscape, several transcriptionally distinct EC subsets exhibit enhanced angiogenic potential and may contribute to EC regeneration during injury. This review synthesizes current knowledge of pulmonary capillary EC heterogeneity, emphasizing arterial-venous polarization of the capillary network, and the identification of reparative EC progenitors within the CAP1 population. We highlight emerging technologies, including EC enrichment strategies, transcriptomics, and epigenomic profiling, that are beginning to resolve rare EC states and functional niches within the alveolar microvasculature. A deeper understanding of capillary EC diversity and lineage dynamics will be essential for identifying therapeutic targets aimed at restoring vascular stability, promoting regenerative angiogenesis, and preserving gas exchange in aging lungs and chronic lung diseases. Ethics: No Human or Animal subjects. Publicly available data sets: Gene Expression Omnibus (GEO)/NCBI: Human ILD data: GSE227136; Mouse data: GSE242065.</p>","PeriodicalId":7593,"journal":{"name":"American journal of physiology. Lung cellular and molecular physiology","volume":" ","pages":"L57-L69"},"PeriodicalIF":3.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148142443","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":"TLR9-mediated innate immune signaling contributes to acetaminophen-induced injury in the developing lung.","authors":"Anastasia Malyshkina, Mack Solar, Natarajan Balasubramaniyan, Lijun Zheng, David J McCulley, Musah Morro, Cadence Seymour, Eniko Sajti, David J Orlicky, Alexander Sosa, Bradford J Smith, Clyde J Wright","doi":"10.1152/ajplung.00085.2026","DOIUrl":"10.1152/ajplung.00085.2026","url":null,"abstract":"<p><p>Acetaminophen (APAP) exposures during human development are common. Emerging epidemiological and experimental evidence links these exposures to subsequent pulmonary morbidity; however, the underlying mechanisms remain incompletely defined. Cell-type-specific expression of the xenobiotic enzyme CYP2E1 is a critical determinant of susceptibility to APAP toxicity. CYP2E1-mediated formation of the reactive metabolite N-acetyl-p-benzoquinone imine (NAPQI) induces mitochondrial injury, which can trigger sterile inflammation through Toll-like receptor 9 (TLR9)-dependent innate immune signaling. The developing mouse lung is particularly vulnerable to APAP exposure at <i>postnatal day 14</i> (P14), a time point within peak alveologenesis that coincides with maximal pulmonary CYP2E1 expression; however, the role of TLR9 signaling in this developmental window has remained unclear. In a preclinical model, wild-type (WT) and TLR9 knockout (TLR9 KO) male and female mice received a single, nonhepatotoxic dose of APAP (140 mg/kg, ip) at P14. Acute lung injury occurred in both genotypes, but TLR9 deficiency reduced proinflammatory target gene (<i>Il1b, Il6</i>) expression and associated STAT3 activation and target gene (<i>Mmp9, Ptgs2, Cxcl2, Bclxl, Pim1</i>) expression. Although APAP-exposed WT mice demonstrated persistent structural and functional abnormalities at P28, attenuation of the early inflammatory response in TLR9 KO mice preserved lung architecture and pulmonary function. These findings identify TLR9-dependent innate immune activation as a mechanistic link between early-life APAP exposure and impaired lung development. The data further suggest that limiting inflammation during the critical window of alveologenesis may preserve normal lung maturation and reduce later pulmonary morbidity. Further studies are warranted to define the clinical relevance of these findings.<b>NEW & NOTEWORTHY</b> Acute lung injury following acetaminophen (APAP) exposures during the key developmental window of alveologenesis has been previously described. Here, we highlight that eliminating TLR9-mediated immune signaling and associated induction of key proinflammatory mediators attenuated impaired lung development and associated dysfunction. We propose that an underlying mechanism linked with sterile inflammation contributes to abnormal pulmonary development following APAP exposure, and that further investigation is necessary for application in a clinical environment.</p>","PeriodicalId":7593,"journal":{"name":"American journal of physiology. Lung cellular and molecular physiology","volume":" ","pages":"L16-L33"},"PeriodicalIF":3.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13273618/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147969666","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":"Hormonal influences on asthma phenotypes and endotypes during the menopausal transition.","authors":"Ashish Kumar, Joe G Zein, Patricia Silveyra","doi":"10.1152/ajplung.00170.2026","DOIUrl":"10.1152/ajplung.00170.2026","url":null,"abstract":"<p><p>Asthma heterogeneity remains a defining challenge driven by multiple factors, including hormonal influences that contribute to distinct phenotypic and endotypic manifestations during the menopausal transition. Fluctuations in sex hormones such as estrogen and progesterone during this period do not merely alter reproductive physiology but they fundamentally modulate immune regulation, airway homeostasis, and inflammatory thresholds in ways that give rise to distinct clinically underrecognized asthma phenotypes and endotypes. This review examines how the hormonal milieu during the menopausal transition, defined as the period marked by changes in menstrual cycle regularity and ending 12 mo after the final menstrual period (menopause), may influence the classical asthma subtypes. We highlight the hormonal dynamics, clinical features of asthma, asthma endotypes and phenotypes, and therapeutic modifiers of asthma during the menopausal transition. Collectively, this review underscores the need to reframe menopause-associated asthma as hormonally driven, biologically distinct subtypes while highlighting the critical gaps in knowledge that must be addressed to develop effective therapeutic strategies for this vulnerable and understudied population.</p>","PeriodicalId":7593,"journal":{"name":"American journal of physiology. Lung cellular and molecular physiology","volume":" ","pages":"L79-L88"},"PeriodicalIF":3.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148203811","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":"A biomimetic miniaturized in vitro model to target early markers of neonatal pulmonary vascular injury.","authors":"Motaharehsadat Heydarian, Ali Doryab, Juan Henao, Benjamin Schubert, Otmar Schmid, Anne Hilgendorff","doi":"10.1152/ajplung.00002.2026","DOIUrl":"10.1152/ajplung.00002.2026","url":null,"abstract":"<p><p>Pulmonary vascular disease (PVD) is a major contributor to morbidity in preterm infants as it is associated with a significant risk to develop pulmonary hypertension, especially in infants diagnosed with prematurity-associated lung disease (PLD), also known as bronchopulmonary dysplasia (BPD). However, the earliest events of vascular injury triggered by postnatal mechanical and oxygen-related stress remain poorly understood, largely due to the limitations of existing in vitro models. We therefore developed a biomimetic, miniaturized pulmonary in vitro perfusion (PIPE) system that integrates pathophysiologically relevant shear stress with controlled oxygen exposure for the exposure of a human coculture of pulmonary microvascular endothelial cells and pulmonary artery smooth muscle cells. Advancing the system to a triple coculture, circulating THP-1 monocytes capture early endothelial-smooth muscle-immune cell interactions. Shear stress alone induced early proliferative and extracellular matrix-related responses in endothelial cells and resulted in enhanced monocyte recruitment without disrupting barrier integrity. When combined with oxygen exposure, the model revealed a dose-dependent injury pattern: moderate hyperoxia [fraction of inspired oxygen ([Formula: see text] = 0.40)] had minimal acute effects, whereas severe hyperoxia ([Formula: see text] = 0.85) impaired endothelial barrier function, increased reactive oxygen species (ROS) production, promoted monocyte transmigration, activated apoptosis (caspase 3), and elevated soluble collagen synthesis. This dynamic in vitro system reveals early drivers in vascular injury and recapitulates key characteristics of PVD, thereby introducing a translational platform for the dissection of disease mechanisms and evaluation of therapeutic strategies targeting vascular injury in the developing lung.<b>NEW & NOTEWORTHY</b> We present a biomimetic, miniaturized in vitro model that replicates key features of neonatal pulmonary vascular injury. By integrating physiologically relevant cues, this platform enables early detection of injury-associated molecular markers and mechanistic interrogation of disease onset. This scalable model offers a powerful tool for studying neonatal lung vascular pathology and for accelerating the discovery of early diagnostic and therapeutic strategies.</p>","PeriodicalId":7593,"journal":{"name":"American journal of physiology. Lung cellular and molecular physiology","volume":" ","pages":"L92-L104"},"PeriodicalIF":3.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148203847","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}