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

{"title":"Lung endothelial cell heterogeneity in health and pulmonary vascular disease.","authors":"Karina Mora Massad, Zhiyu Dai, Irina Petrache, Corey E Ventetuolo, Tim Lahm","doi":"10.1152/ajplung.00296.2024","DOIUrl":"10.1152/ajplung.00296.2024","url":null,"abstract":"<p><p>Lung endothelial cells (ECs) are essential for maintaining organ function and homeostasis. Despite sharing some common features with ECs from organ systems, lung ECs exhibit significant heterogeneity in morphology, function, and gene expression. This heterogeneity is increasingly recognized as a key contributor to the development of pulmonary diseases like pulmonary hypertension (PH). In this mini-review, we explore the evolving understanding of lung EC heterogeneity, particularly through the lens of single-cell RNA sequencing (scRNA-seq) technologies. These advances have provided unprecedented insights into the diverse EC subpopulations, their specific roles, and the disturbances in their homeostatic functions that contribute to PH pathogenesis. In particular, these studies identified novel and functionally distinct cell types such as aerocytes and general capillary ECs that are critical for maintaining lung function in health and disease. In addition, multiple novel pathways and mechanisms have been identified that contribute to aberrant pulmonary vascular remodeling in PH. Emerging techniques like single-nucleus RNA sequencing and spatial transcriptomics have further pushed the field forward by discovering novel disease mediators. As research continues to leverage these advanced techniques, the field is poised to uncover novel EC subtypes and disease mechanisms, paving the way for new therapeutic targets in PH and other lung diseases.</p>","PeriodicalId":7593,"journal":{"name":"American journal of physiology. Lung cellular and molecular physiology","volume":" ","pages":"L877-L884"},"PeriodicalIF":3.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12116231/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142942655","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":"Allergic airway inflammation amplifies mast cell responses in isolated guinea pig intralobular bronchi.","authors":"Mu Nie, Jielu Liu, Yujiao Xiang, Anthony Wong, Emma Hendriks, Gunnar Nilsson, Jesper Säfholm, Mikael Adner","doi":"10.1152/ajplung.00422.2024","DOIUrl":"10.1152/ajplung.00422.2024","url":null,"abstract":"<p><p>Excessive uncontrolled airway narrowing is the main cause of the symptoms in asthma, yet the reasons behind this problem are still elusive. As mechanistic studies of isolated airways from asthmatic individuals are almost impossible to perform, the aim of this study was to investigate the contractile responses in intralobular bronchi (ILBs) isolated from a guinea pig asthma model. These distal airways are surrounded by parenchymal tissue and resemble functional characteristics of human bronchi. Isolated ILBs were mounted in myographs to measure smooth muscle reactions. To avoid the irreversible postmortem bronchoconstriction, lungs were filled with ice-cold buffer solution containing 1 µM salbutamol followed by 48 hours of incubation of the isolated ILBs. Pharmacological characterization of ILBs from naïve guinea pigs showed that prostaglandin E₂ induced mild relaxation, whereas histamine, carbachol, leukotriene D₄, and the thromboxane A₂ mimetic U46619 caused robust contractions. Although the responses to contractile agonists (histamine, carbachol, and leukotriene D₄) were similar, the contractile responses to house dust mite extract (HDM) in ILBs from HDM-sensitized and challenged guinea pigs were significantly greater than those from sensitized-only control guinea pigs. Similarly to isolated human small airways, the antigen response was abolished by inhibitors to mast cell mediators such as histamine, leukotrienes, and prostanoids. This study presents, for the first time, an investigation of bronchial responses using a guinea pig asthma model, examining airways with pathophysiological features similar to those of asthmatic individuals and comparing them to matched controls. Moreover, the results suggest the potential of mast cells in the development of asthma.<b>NEW & NOTEWORTHY</b> A protocol to avoid postmortem constriction in isolated intralobular bronchi from guinea pigs was established. A new model makes it possible to investigate bronchial responses in airways with asthmatic features. Increased responses in bronchi from the guinea pig asthma model suggest the importance of mast cells in asthma.</p>","PeriodicalId":7593,"journal":{"name":"American journal of physiology. Lung cellular and molecular physiology","volume":" ","pages":"L638-L649"},"PeriodicalIF":3.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656116","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":"TrkB signaling promotes alveolar capillary angiogenesis following perinatal hyperoxic damage.","authors":"Qing Ma, Hanxiang Liu, Ming Liu, Yanli Wang, Yutian Lai, Yuchen Zhao, Ming Li, Yanru Liu, Chong Ma, Jiashuang Lai, Hanmin Liu, Hua He, Fei Sun, Xinhua Lin","doi":"10.1152/ajplung.00334.2023","DOIUrl":"10.1152/ajplung.00334.2023","url":null,"abstract":"<p><p>Impaired angiogenesis characterized by the reduced proliferation of pulmonary endothelial cells leads to reduced capillary density in patients with bronchopulmonary dysplasia (BPD). In a mouse model of BPD, perinatal hyperoxic injury decreases the number of the recently identified lung capillary stem cells termed as general capillary (gCap) cells, along with the specific reduction of <i>Ntrk2</i>, which encodes for tropomyosin receptor kinase B (TrkB), within this subpopulation. Herein, we determine whether TrkB signaling is required for perinatal gCap cell proliferation and pulmonary angiogenesis in a hyperoxia mouse BPD model. TrkB activation by brain-derived neurotrophic factor (BDNF) treatment led to enhanced tube-forming ability of endothelial cells in vitro. In vivo treatment of mice with BDNF increased the proliferation of gCap cells and alleviated gCap loss caused by hyperoxic injury. Conversely, inhibition of TrkB signaling disrupted the tube formation of endothelial cells and exaggerated the vascular endothelial damage caused by hyperoxia. We further show that MAPK/ERK signaling acts downstream of TrkB to modulate pulmonary angiogenesis. These data indicate that TrkB signaling plays a critical role in pulmonary angiogenesis upon perinatal lung injury, supporting the concept that TrkB activation might be a potential therapeutic for preserving endothelial cells for lung diseases associated with prematurity.<b>NEW & NOTEWORTHY</b> The present study highlights the essential role of BDNF/TrkB signaling in capillary endothelial cell proliferation and preserving alveolar architecture during perinatal hyperoxic lung injury, supporting the concept that activation of TrkB/MAPK/ERK signaling might be a strategy to restore alveolar angiogenesis for preterm infants at risk of BPD.</p>","PeriodicalId":7593,"journal":{"name":"American journal of physiology. Lung cellular and molecular physiology","volume":" ","pages":"L617-L630"},"PeriodicalIF":3.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690850","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":"Flavor chemicals in vaping products induce pulmonary dendritic cell maturation.","authors":"Félix Tremblay, Judith Fortier, Marie Pineault, Nadia Milad, Noémie de Villiers, Magalie Trudel, Ariane Lechasseur, Joanie Routhier, Marie-Josée Beaulieu, Sophie Aubin, Mathieu C Morissette","doi":"10.1152/ajplung.00305.2024","DOIUrl":"10.1152/ajplung.00305.2024","url":null,"abstract":"<p><p>Vaping products contain numerous flavor chemicals that are known immunological sensitizers associated with the elicitation of immune-mediated hypersensitivity responses. Therefore, we investigated the immune response associated with sensitizing flavor chemicals in vaping liquids and focused on dendritic cell maturation as it is a crucial early cellular event of the sensitization immunological cascade. Bone marrow-derived dendritic cells (BMDDCs) were used to assess induction of dendritic cell maturation upon treatment with unique flavor vaping liquids and aerosol condensates. Female BALB/c mice were exposed 2 h/day for 4 days to nicotine-free vaping aerosols containing a mixture of citral, cinnamaldehyde, dihydrocoumarin, and vanillin. In vitro experiments indicate that cinnamaldehyde and citral, but not vaping liquid solvents, dihydrocoumarin and vanillin, are capable of inducing BMDDC maturation. In vivo, we observed an increase in the expression of maturation marker MHC class II (MHCII) on conventional dendritic cells (cDCs) in the lung tissue of mice exposed to flavored vaping aerosols compared with exposure controls. Maturation was specifically observed on CD11b+ cDCs and not CD103+ cDCs. No significant changes were observed for macrophages, neutrophils, B and T lymphocytes in the lung tissue, and bronchoalveolar lavage. Also, we found that regulatory T lymphocytes had decreased expression of CD25 in mice exposed to flavored vaping aerosols compared with exposure controls. These findings indicate that flavored chemicals can lead to rapid dendritic cell maturation in vitro and in vivo, representing an early cellular event related to respiratory sensitization and pulmonary disease.<b>NEW & NOTEWORTHY</b> Current research on vaping do not report major impact on cellular immune response. However, our findings support that flavored vaping aerosol exposure can lead to rapid modulation of dendritic cells and regulatory T lymphocytes in the lungs and extrapulmonary location. Although our findings were obtained in acute settings, they entertain the possibility that chronic exposure to vaping aerosols could progressively trigger the immunological cascade responsible for the development of serious lung diseases resembling hypersensitivity pneumonitis.</p>","PeriodicalId":7593,"journal":{"name":"American journal of physiology. Lung cellular and molecular physiology","volume":" ","pages":"L685-L697"},"PeriodicalIF":3.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770853","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":"Cannabis consumption conundrum: weighing the risks of vaping and smoking.","authors":"Alexia Perryman, Laura E Crotty Alexander","doi":"10.1152/ajplung.00111.2025","DOIUrl":"10.1152/ajplung.00111.2025","url":null,"abstract":"","PeriodicalId":7593,"journal":{"name":"American journal of physiology. Lung cellular and molecular physiology","volume":" ","pages":"L698-L699"},"PeriodicalIF":3.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787435","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":"Involvement of ryanodine receptors in the contraction of small pulmonary veins.","authors":"Francisca Varas, Marcelo Fonseca, Natalia Astudillo, Damian Gorski, Danielle Harrison, Carol San Martin, Santiago Ramirez, Mauricio Henriquez","doi":"10.1152/ajplung.00375.2024","DOIUrl":"10.1152/ajplung.00375.2024","url":null,"abstract":"<p><p>The contractile mechanisms involving calcium ions (Ca²⁺) regulation in smooth muscle cells (SMCs) of small intrapulmonary veins (SPVs) are not yet fully understood despite being relevant in lung physiology. Studies on vasoconstriction induced by physiological agonists have not been sufficient to understand the role of ryanodine receptors (RyRs). These calcium channels release Ca²⁺ from the sarcoplasmic reticulum (SR), within the contraction process of SPV. We hypothesize that RyRs act in a stimulus-dependent manner. Here, we first analyzed existing single-cell RNA sequencing datasets of human and rat lungs to evaluate the expression of RyRs in SMC and other cell types, followed by functional studies to assess SPV contraction using an ex vivo precision-cut lung slice (PCLS) model. To understand the participation of RyRs downstream in contraction pathways, different contractile agents were combined with RyRs agonists and antagonists. We demonstrated that RyRs are expressed in lung smooth muscle cells of humans and rats, participating in SPV contraction likely through the Gq-coupled protein receptor pathway.<b>NEW & NOTEWORTHY</b> The results indicate that RyR2 would be the most relevant isoform in SPV contraction induced by depolarization, whereas RyR1 and RyR3 would participate in the contractile mechanism induced by GqPCR agonists. It is worth noting that based on the scRNA seq studies, RyR1 was shown to be the less expressed isoform in SMCs in the rat lung, which indicates that RyR2 and RyR3 may be the most relevant isoforms participating in the contraction of SPV.</p>","PeriodicalId":7593,"journal":{"name":"American journal of physiology. Lung cellular and molecular physiology","volume":" ","pages":"L661-L668"},"PeriodicalIF":3.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778599","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":"Pulmonary capillary blood volume and diffusing membrane capacity during exercise in humans: role of pulmonary artery pressure.","authors":"Andrew W D'Souza, Andrew R Brotto, Bronwen Hicks, Eli Bok, Jason Weatherald, Sean Van Diepen, Michael K Stickland","doi":"10.1152/ajplung.00358.2024","DOIUrl":"10.1152/ajplung.00358.2024","url":null,"abstract":"<p><p>During exercise, lung diffusing capacity for carbon monoxide (DL_CO), pulmonary capillary blood volume (V_c), and diffusing membrane capacity (D_M) increase secondary to a rise in pulmonary artery pressure (PAP) and central blood volume mobilization. Although the role of central blood volume on DL_CO is well established, the impact of PAP on DL_CO, V_c, and D_M during exercise is less clear. Based on previous work, we tested the hypothesis that acute increases in PAP will potentiate exercise DL_CO via increases in D_M. Fifteen healthy young adults (7 females; age: 24 ± 4 yr) completed two bouts of cycling exercise at 60 W, with (CUFF) or without (CON) bilateral thigh cuff inflation pressurized to 90 mmHg. The multiple fractions of the inspired O₂-DL_CO method were used to determine DL_CO, V_c, and D_M at baseline and during both exercise conditions alongside estimates of cardiac output (Q̇_c; impedance cardiography) and right ventricular systolic pressure (RVSP; echocardiography). CUFF exercise resulted in a larger increase in RVSP (CUFF: 44.7 ± 6.1 vs. CON: 38.9 ± 5.5 mmHg; <i>P</i> = 0.036) but not Q̇_c (<i>P</i> = 0.644) or V̇o₂ (<i>P</i> = 0.976) compared with CON. DL_CO was higher during the CUFF exercise (CUFF: 41 ± 6 vs. CON: 38 ± 6 mL/min/mmHg; <i>P</i> = 0.001) and was mediated by increases in D_M (CUFF: 138 ± 55 vs. CON: 90 ± 39 mL/min/mmHg; <i>P</i> = 0.032), not V_c (CUFF: 85 ± 18 vs. CON: 98 ± 27 mL/min/mmHg; <i>P</i> = 0.820). Increases in RVSP were positively related to D_M (<i>r</i>_rm = 0.82; <i>P</i> = 0.024) but inversely related to V_c (<i>r</i>_rm = -0.80, <i>P</i> = 0.029). Collectively, these data indicate that PAP primarily contributes to DL_CO during low-intensity exercise via increases in capillary recruitment (i.e., D_M).<b>NEW & NOTEWORTHY</b> Pulmonary artery pressure contributes to DL_CO recruitment during exercise. However, it is unclear how pulmonary artery pressure impacts the pulmonary microcirculatory adjustments that comprise DL_CO, namely V_c and D_M. Using subsystolic occlusion of the locomotor muscles during exercise to induce increases in pulmonary artery pressure, without changes in cardiac output or metabolic demand, we demonstrate that pulmonary artery pressure contributes to DL_CO during exercise via heightened capillary recruitment (D_M).</p>","PeriodicalId":7593,"journal":{"name":"American journal of physiology. Lung cellular and molecular physiology","volume":" ","pages":"L631-L637"},"PeriodicalIF":3.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662038","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":"Succinate aggravates pulmonary fibrosis through the succinate/SUCNR1 axis.","authors":"Rishi Rajesh, Agnes Anna Mooslechner, Hannah Schweighofer, Svetlana Pahernik, Ilse Lanz, Reham Atallah, Wolfgang Platzer, Clemens Aigner, Alberto Benazzo, Stefano Angiari, Leigh Marsh, Grazyna Kwapiszewska, Akos Heinemann, Thomas Bärnthaler","doi":"10.1152/ajplung.00286.2024","DOIUrl":"10.1152/ajplung.00286.2024","url":null,"abstract":"<p><p>Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease that leads to destruction of alveoli and replacement by fibrotic tissue. Metabolic profiling of lung tissue and serum from patients with IPF has revealed that levels of tricarboxylic acid cycle metabolites such as succinate are altered in patients with IPF. In our study, we aim to evaluate the role of succinate and its receptor-succinate receptor 1 (SUCNR1) in the pathogenesis of lung fibrosis, with a focus on fibroblasts, a central cell in IPF. SUCNR1 expression was investigated by using Western blots, qPCR, and in situ hybridisation. In vitro assays with IPF and normal human lung fibroblasts (NHLF) were used to evaluate the effect of succinate treatment on the expression of fibrotic markers, fibroblast-myofibroblast transition, apoptosis, and signaling mechanisms. Studies with the bleomycin mouse model of pulmonary fibrosis were used to evaluate the effect of succinate in vivo. Several cell types in the lung express SUCNR1 including alveolar type II cells, fibroblasts, and macrophages. In IPF patient fibroblasts, succinate treatment increased the expression of fibrosis-associated markers, such as alpha-smooth muscle actin and collagen. Moreover, succinate exaggerated transforming growth factor-beta (TGF-β)-mediated fibroblast-to-myofibroblast transition in NHLF. In vivo, succinate treatment significantly increased collagen accumulation in the lung and enhanced weight loss in bleomycin-treated mice. Importantly, succinate-mediated elevation of fibrosis-associated markers was lost upon knockdown of SUCNR1 or inhibition of ERK activation in IPF patient-derived fibroblasts. Succinate exerted profibrotic effects in vitro and in vivo. Thus, SUCNR1 antagonism may be a potential therapeutic target for the treatment of IPF.<b>NEW & NOTEWORTHY</b> This paper highlights the role of the succinate/SUCNR1 axis in pulmonary fibrosis. Receptor activation leads to profibrotic changes in IPF patient-derived fibroblasts. This finding could also be replicated in a mouse model of pulmonary fibrosis.</p>","PeriodicalId":7593,"journal":{"name":"American journal of physiology. Lung cellular and molecular physiology","volume":" ","pages":"L671-L684"},"PeriodicalIF":3.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7617945/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727469","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":"Effect of age, COPD severity, and cigarette smoke exposure on bronchial epithelial barrier function.","authors":"Kingsley Okechukwu Nwozor, Tillie-Louise Hackett, Qing Chen, Chen Xi Yang, Sheila Patricia Aguilar Lozano, XinZi Zheng, May Al-Fouadi, Tessa M Kole, Alen Faiz, Rashad Mohammad Mahbub, Dirk-Jan Slebos, Karin Klooster, Wim Timens, Maarten van den Berge, Corry-Anke Brandsma, Irene H Heijink","doi":"10.1152/ajplung.00223.2024","DOIUrl":"10.1152/ajplung.00223.2024","url":null,"abstract":"<p><p>We investigated the effect of age, cigarette smoke, and chronic obstructive pulmonary disease (COPD) severity on epithelial barrier function. Primary bronchial epithelial cells (PBECs) were obtained from bronchial brushings in eight younger and eight older never-smokers; seven older ex-smokers without COPD, eight patients with COPD Global Initiative for Chronic Obstructive Lung Disease (GOLD) I-III and six patients with COPD GOLD IV, and cultured in the absence/presence of cigarette smoke extract (CSE). Epithelial barrier function was assessed by electric resistance sensing and expression of junctional and antioxidant genes/proteins quantified by qPCR/immunodetection. Epithelial barrier function was comparable between PBECs from younger and older never-smokers. PBECs from ex-smokers had significantly lower barrier function compared with never-smokers, with a further decrease in COPD GOLD IV. CSE decreased epithelial barrier function from which PBECs from never-smokers, but not ex-smokers with and without COPD, recovered. Restoration of barrier function was accompanied by increased expression of barrier and antioxidant genes. At baseline, PBECs from ex-smokers with and without COPD had higher expression of junctional and antioxidant genes compared with never-smokers. However, exposure to CSE increased antioxidant (<i>SOD1-3</i>, <i>CAT)</i> gene expression only in PBECs from never-smokers and ex-smokers without COPD. In conclusion, our data indicate that cigarette smoking and COPD severity are associated with reduced epithelial barrier function, which is potentially driven by an imbalance in the antioxidant response.<b>NEW & NOTEWORTHY</b> Cigarette smoking and chronic obstructive pulmonary disease (COPD) severity are associated with reduced epithelial barrier function that is potentially driven by an imbalance in the antioxidant response.</p>","PeriodicalId":7593,"journal":{"name":"American journal of physiology. Lung cellular and molecular physiology","volume":"328 5","pages":"L724-L737"},"PeriodicalIF":3.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958766","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":"Selenium modulates perinatal pulmonary vascular responses to hyperoxia.","authors":"Maxwell Mathias, Hua Zhong, Paul T Pierce, Lynette K Rogers, Lora Bailey-Downs, Abhrajit Ganguly, Trent E Tipple","doi":"10.1152/ajplung.00381.2024","DOIUrl":"10.1152/ajplung.00381.2024","url":null,"abstract":"<p><p>Mammalian lung development depends on growth and differentiation of both endothelial and epithelial subpopulations to allow for gas exchange. Premature infants are born with developmentally immature lungs and often require supplemental oxygen (O₂) to survive. Excess O₂ can lead to oxidative stress, which damages the pulmonary vasculature and contributes to bronchopulmonary dysplasia (BPD). Selenoproteins are critical for detoxifying reactive oxygen intermediates. Selenoprotein production is dependent upon adequate selenium (Se) levels. Using a model of perinatal Se deficiency in C3H/HeN mice, we assessed the impacts of Se status and postnatal O₂ exposure on lung vascular development at P14. Furthermore, we compared the transcription of endothelial subpopulation and endothelial-to-mesenchymal transition markers in control and O₂-exposed lungs using RNAseq from P3 mouse lungs. Transcriptional changes identified from RNAseq were validated using qRT-PCR. Se deficiency and O₂ exposure independently decreased the number of pulmonary arterioles at P14. In addition, Se deficiency and O₂ exposure decreased transcription of the general capillary endothelial cell markers <i>Aplnr</i> and <i>Ptprb.</i> These findings support the hypothesis that Se deficiency confers susceptibility to hyperoxic pulmonary vascular maldevelopment as is seen in BPD.<b>NEW & NOTEWORTHY</b> The data demonstrate a reduction in the number of pulmonary blood vessels in the setting of perinatal selenium deficiency that is exacerbated by postnatal O₂ exposure. RNA analysis of peripheral lung tissue indicated that changes in vessel density were associated with alterations in the transcription of genes responsible for maintenance of endothelial phenotype and homeostasis in our experimental bronchopulmonary dysplasia model.</p>","PeriodicalId":7593,"journal":{"name":"American journal of physiology. Lung cellular and molecular physiology","volume":" ","pages":"L716-L723"},"PeriodicalIF":3.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770837","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}