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American Journal of Physiology. Lung Cellular and Molecular Physiology

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https://read.qxmd.com/read/30785346/erythropoietin-inhalation-enhances-adult-canine-alveolar-capillary-formation-following-pneumonectomy
#1
D Merrill Dane, Cuneyt Yilmaz, Dipendra Gyawali, Roshni Iyer, Jyothi U Menon, Kytai T Nguyen, Priya Ravikumar, Aaron S Estrera, Connie C W Hsia
Paracrine erythropoietin (EPO) signaling in the lung recruits endothelial progenitor cells, promotes cell maturation and angiogenesis , and is upregulated during canine post-pneumonectomy (PNX) compensatory lung growth. To determine whether inhalational delivery of exogenous EPO augments endogenous post-PNX lung growth, adult canines underwent right PNX and received, via a permanent tracheal stoma, weekly nebulization of recombinant human EPO-containing nanoparticles or empty nanoparticles (control) for 16 weeks...
February 20, 2019: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://read.qxmd.com/read/30785345/cellular-senescence-in-the-lung-across-the-age-spectrum
#2
Pavan Parikh, Sarah Wicher, Karl Khandalavala, Christina M Pabelick, Rodney D Britt, Y S Prakash
Cellular senescence results in cell cycle arrest with secretion of cytokines, chemokines, growth factors and remodeling proteins (senescence associated secretory phenotype; SASP) that have autocrine and paracrine effects on the tissue microenvironment. SASP can promote remodeling, inflammation, infectious susceptibility, angiogenesis and proliferation, while hindering tissue repair and regeneration. While the role of senescence and contributions of senescent cells are increasingly recognized in the context of aging and a variety of disease states, relatively less is known regarding the portfolio and influences of senescent cells in normal lung growth and aging per se, or in the induction or progression of lung diseases across the age spectrum such as bronchopulmonary dysplasia, asthma, COPD, or pulmonary fibrosis...
February 20, 2019: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://read.qxmd.com/read/30785344/monocrotaline-pyrrole-induces-pulmonary-endothelial-damage-through-binding-to-and-release-from-erythrocytes-in-lung-during-venous-blood-reoxygenation
#3
Rui Xiao, Liping Zhu, Yuan Su, Jiwei Zhang, Yankai Lu, Jiansha Li, Tao Wang, Jing Fang, Zhi-Cheng Jing, Jocelyn Dupuis, Shengquan Luo, Qinghua Hu
Monocrotaline has been widely used to establish an animal model of pulmonary hypertension, most frequently in rats. An important feature of this model resides in the selectivity of monocrotaline injury towards the pulmonary vascular endothelium versus the systemic vasculature when administrated at standard dosage. The toxic metabolite of monocrotaline, monocrotaline pyrrole, is transported by erythrocytes. This study aimed to reveal whether partial pressure of oxygen of blood determined the binding and release of monocrotaline pyrrole from erythrocytes in rats with one subcutaneous injection of monocrotatline at the standard dosage of 60 mg/Kg...
February 20, 2019: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://read.qxmd.com/read/30785343/delayed-resolution-of-bleomycin-induced-pulmonary-fibrosis-in-absence-of-mmp13-collagenase-3
#4
Sandra Cabrera, Mariana Maciel, Daniel Hernandez-Barrientos, Jazmin Calyeca, Miguel Gaxiola, Moisés Selman, Annie Pardo
MMP13 deficiency in pulmonary fibrosis have described contradictory phenotypes on inflammatory and fibrotic responses after lung injury and its role during lung fibrosis resolution is still undefined. MMP13 has been considered the main collagenase in rodents, and the remodeling of fibrillar collagen is widely attributed to the action of this enzyme. In this study we aimed to explore the role of MMP13 during lung fibrosis progression and resolution. Lung fibrosis was induced by intratracheal instillation, and inflammatory, fibrotic and resolution stages were evaluated in Mmp13 null and WT mice...
February 20, 2019: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://read.qxmd.com/read/30758992/exhaled-breath-metabolomics-reveals-a-pathogen-specific-response-in-a-rat-pneumonia-model-for-two-human-pathogenic-bacteria-a-proof-of-concept-study
#5
Pouline M P van Oort, Paul Brinkman, Gitte Slingers, Gudrun Koppen, Adrie Maas, Joris J T H Roelofs, Ronny Schnabel, Dennis C Bergmans, Marc Raes, Roy Goodacre, Stephen J Fowler, Marcus J Schultz, Lieuwe D Bos, BreathDx Consortium
INTRODUCTION: Volatile organic compounds (VOCs) in breath can reflect host and pathogen metabolism and might be used to diagnose pneumonia. We hypothesized that rats with Streptococcus pneumoniae ( SP) or Pseudomonas aeruginosa ( PA) pneumonia can be discriminated from uninfected controls by thermal desorption - gas chromatography - mass-spectrometry (TD-GC-MS) and selected ion flow tube - mass spectrometry (SIFT-MS) of exhaled breath. METHODS: Male adult rats ( n=50) received an intra-tracheal inoculation of 1) 200 µL saline, 2) 1x107 colony forming units (CFU) of SP or 3) 1x107 CFU of PA...
February 13, 2019: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://read.qxmd.com/read/30758991/extracellular-vesicles-another-compartment-for-the-second-messenger-cyclic-adenosine-monophosphate-camp
#6
Sarah L Sayner, Chung-Sik Choi, Marcy E Maulucci, Ramila Kc, Chun Zhou, April K Scruggs, Thomas Yarbrough, Leslie Anne Hargett Blair, Judy A C King, Roland Seifert, Volkhard Kaever, Natalie N Bauer
The second messenger, cAMP, is highly compartmentalized to facilitate signaling specificity. Extracellular vesicles (EVs) are submicron, intact vesicles released from many cell types that can act as biomarkers or be involved in cell-to-cell communication. While it is well recognized that EVs encapsulate functional proteins and RNAs/miRNAs, currently it is unclear whether cyclic nucleotides are encapsulated within EVs to provide an additional second messenger compartment. Using ultracentrifugation, EVs were isolated from the culture medium of unstimulated systemic and pulmonary endothelial cells...
February 13, 2019: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://read.qxmd.com/read/30758990/prostaglandin-e2-inhibits-pro-fibrotic-function-of-human-pulmonary-fibroblasts-by-disrupting-ca2-signaling
#7
Subhendu Mukherjee, Wei Sheng, Alexander Michkov, Krishna Sriarm, Rui Sun, Anna Dvorkin-Gheva, Paul A Insel, Luke J Janssen
We have shown that calcium (Ca2+ ) oscillations in human pulmonary fibroblasts (HPFs) contribute to pro-fibrotic effects of TGFβ and that disruption of these oscillations blunts features of pulmonary fibrosis. Prostaglandin E2 (PGE2 ) exerts anti-fibrotic effects in the lung but the mechanisms for this action are not well defined. We thus sought to explore interactions between PGE2 and the pro-fibrotic agent transforming growth factor beta (TGFβ) in pulmonary fibroblasts (PFs) isolated from patients with or without idiopathic pulmonary fibrosis (IPF)...
February 13, 2019: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://read.qxmd.com/read/30724100/galectin-3-is-expressed-in-vascular-smooth-muscle-cells-and-promotes-pulmonary-hypertension-through-changes-in-proliferation-apoptosis-and-fibrosis
#8
Scott A Barman, Xueyi Li, Stephen Haigh, Dmitry Kondrikov, Keyvan Mahboubi, Zsuzsanna Bordan, David W Stepp, Jiliang Zhou, Yusi Wang, Daniel S Weintraub, Peter Traber, William Snider, Danny Jonigk, Jennifer C Sullivan, G Ryan Crislip, Joshua T Butcher, Jennifer Thompson, Yunchao Su, Feng Chen, David J R Fulton
A defining characteristic of Pulmonary Hypertension (PH) is the extensive remodeling of pulmonary arteries (PA) that results in progressive increases in vascular resistance and stiffness and eventual failure of the right ventricle. There is no cure for PH and identification of novel molecular mechanisms that underlie increased proliferation, reduced apoptosis and excessive extracellular matrix production in pulmonary artery smooth muscle cells (PASMC) is a vital objective. Galectin-3 (Gal-3) is a chimeric lectin and potent driver of many aspects of fibrosis, but its role in regulating PASMC behavior in PH remains poorly understood...
February 6, 2019: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://read.qxmd.com/read/30724099/fourth-generation-e-cigarette-vaping-induces-transient-lung-inflammation-and-gas-exchanges-disturbances-results-from-two-randomized-clinical-trials
#9
Martin Chaumont, Philippe van de Borne, Alfred Bernard, Alain Van Muylem, Guillaume Deprez, Julien Ullmo, Eliza Starczewska, Rachid Briki, Quentin de Hemptinne, Wael Zaher, Nadia Debbas
BACKGROUND: When heated by an electronic cigarette, propylene glycol and glycerol produce a nicotine-carrying-aerosol. This hygroscopic/hyperosmolar aerosol can deposit deep within the lung. Whether these deposits trigger local inflammation and disturb pulmonary gas exchanges is not known. AIMS: To assess the acute effects of high-wattage electronic cigarette vaping with or without nicotine on lung inflammation biomarkers, transcutaneous gas tensions, and pulmonary function tests in young and healthy tobacco-smokers...
February 6, 2019: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://read.qxmd.com/read/30724098/resolvin-d1-attenuates-mechanical-stretch-induced-pulmonary-fibrosis-via-epithelial-mesenchymal-transition-emt
#10
Yiyi Yang, Lisha Hu, Haifa Xia, Lin Chen, Shunan Cui, Yaxin Wang, Ting Zhou, Wei Xiong, Limin Song, Shengnan Li, Shangwen Pan, Jiqian Xu, Min Liu, Hairong Xiao, Lu Qin, You Shang, Shanglong Yao
Mechanical ventilation-induced pulmonary fibrosis plays an important role in the high mortality rate of acute respiratory distress syndrome (ARDS). Resolvin D1 (RvD1) displays potent proresolving activities. Epithelial-mesenchymal transition (EMT) has been proven to be an important pathological feature of lung fibrosis. This study aimed to investigate whether RvD1 can attenuate mechanical ventilation-induced lung fibrosis. Human lung epithelial cells (BEAS-2B) were pretreated with RvD1 for 30 min and exposed to acid for 10 min before being subjected to mechanical stretch for 48 hours...
February 6, 2019: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://read.qxmd.com/read/30724097/regulation-of-ovarian-cancer-g-protein-coupled-receptor-ogr1-expression-and-signaling
#11
Ajay P Nayak, Tonio Pera, Deepak A Deshpande, James V Michael, Jennifer R Liberato, Shi Pan, Eric Tompkins, Henry P Morelli, Roslyn Yi, Nadan Wang, Raymond B Penn
Ovarian cancer G protein-coupled receptor 1 (OGR1) is a recently deorphanized G protein-coupled receptor shown to signal in response to low extracellular pH (↓pHo) or certain benzodiazepines. The pleiotropic nature of OGR1 signaling in human airway smooth muscle (HASM) cells suggests OGR1 is a potential therapeutic target for the management of obstructive lung diseases. However, the basic pharmacological and regulatory features of OGR1 remain poorly understood. We employed model systems of heterologously-expressed (HEK293 cells) or endogenous (HASM) OGR1 to assess changes in expression, subcellular localization, and signaling capabilities following acute or chronic treatment with ↓pHo or the benzodiazepines lorazepam and sulazepam...
February 6, 2019: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://read.qxmd.com/read/30702346/mesothelial-mobilization-in-the-developing-lung-and-heart-differs-in-timing-quantity-and-pathway-dependency
#12
Timo H Lüdtke, Carsten Rudat, Jennifer Kurz, Regine Häfner, Franziska Greulich, Irina Wojahn, Nurullah Aydoğdu, Tamrat M Mamo, Marc-Jens Kleppa, Mark-Oliver Trowe, Tobias E Bohnenpoll, Makoto Mark Taketo, Andreas Kispert
The mesothelial lining of the lung, the visceral pleura, and of the heart, the epicardium, derive from a common multi-potent precursor tissue, the mesothelium of the embryonic thoracic cavity that also contributes to organ-specific mesenchymal cell types. Insight into mesothelial mobilization and differentiation has prevailed in the developing heart while the mesenchymal transition and fate of the visceral pleura is poorly understood. Here, we use the fact that the early mesothelium of both the lung and the heart expresses the transcription factor gene Wt1, to comparatively analyze mesothelial mobilization in the two organs by a genetic cre-loxPbased conditional approach...
January 31, 2019: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://read.qxmd.com/read/30702345/small-hairpin-rna-and-pharmacological-targeting-of-neutral-sphingomyelinase-prevents-diaphragm-weakness-in-rats-with-heart-failure-and-reduced-ejection-fraction
#13
Philip D Coblentz, Bumsoo Ahn, Linda F Hayward, Jeung-Ki Yoo, Demetra D Christou, Leonardo F Ferreira
Heart failure with reduced ejection fraction (HFREF) increases neutral sphingomyelinase (NSMase) activity, mitochondrial reactive oxygen species emission (ROS), and causes diaphragm weakness. We tested whether a systemic pharmacologic NSMase inhibitor or short-hairpin RNA (shRNA) targeting NSMase isoform 3 (NSMase3) would prevent diaphragm abnormalities induced by HFREF caused by myocardial infarction. In the pharmacological intervention, we used intraperitoneal injection of GW4869 or vehicle. In the genetic intervention, we injected adeno-associated virus serotype 9 (AAV9) containing targeting NSMase3 or a scrambled sequence directly into the diaphragm...
January 31, 2019: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://read.qxmd.com/read/30702344/genetic-inactivation-of-the-phospholipase-a2-activity-of-peroxiredoxin-6-in-mice-protects-against-lps-induced-acute-lung-injury
#14
Jose Pablo Vazquez-Medina, Jian-Qin Tao, Prial Patel, Renata Bannitz-Fernandes, Chandra Dodia, Elena M Sorokina, Sheldon I Feinstein, Shampa Chatterjee, Aron B Fisher
Peroxiredoxin 6 (Prdx6) is a multi-functional enzyme that serves important anti-oxidant roles by scavenging hydroperoxides and reducing peroxidized cell membranes. Prdx6 also plays a key role in cell signaling by the activation of NADPH oxidase,type 2 (Nox2) through its phospholipase A2 (aiPLA2) activity. Nox2 generation of O2.-, in addition to signaling, can contribute to oxidative stress and inflammation such as during sepsis-induced acute lung injury (ALI). To evaluate a possible role of Prdx6-aiPLA2 activity in the pathophysiology of ALI, wild type (WT) and Prdx6-D140A mice which lack aiPLA2 but retain peroxidase activity were administered intraperitoneal LPS...
January 31, 2019: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://read.qxmd.com/read/30702343/pharmacological-activation-of-liver-x-receptor-during-cigarette-smoke-exposure-adversely-affects-alveolar-macrophages-and-pulmonary-surfactant-homeostasis
#15
Éric Jubinville, Joanie Routhier, Michaël Maranda-Robitaille, Marie Pineault, Nadia Milad, Maude Talbot, Marie-Josée Beaulieu, Sophie Aubin, Marie-Ève Paré, Mathieu Laplante, Mathieu C Morissette
BACKGROUND: Smoking alters pulmonary reverse lipid transport and leads to intracellular lipid accumulation in alveolar macrophages. We investigated whether stimulating reverse lipid transport with an agonist of the Liver X receptor (LXR) would help alveolar macrophages limit lipid accumulation and dampen lung inflammation in response to cigarette smoke. METHODS: Mice were exposed to cigarette smoke and treated intraperitonealy with the LXR agonist T0901317. Expression of lipid capture and lipid export genes was assessed in lung tissue and alveolar macrophages...
January 31, 2019: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://read.qxmd.com/read/30702342/cd36-mediates-albumin-transcytosis-by-dermal-but-not-lung-microvascular-endothelial-cells-role-in-fatty-acid-delivery
#16
Hira Raheel, Siavash Ghaffari, Negar Khosraviani, Victoria Mintsopoulos, Derek Auyeung, Changsen Wang, Yun Hye Kim, Brendan Mullen, Hoon-Ki Sung, May Ho, Gregory Fairn, Dante Neculai, Maria Febbraio, Bryan Heit, Warren L Lee
In healthy blood vessels, albumin crosses the endothelium to leave the circulation by transcytosis. However, little is known about the regulation of albumin transcytosis or how it differs in different tissues; its physiological purpose is also unclear. Using total internal reflection fluorescence microscopy, we quantified transcytosis of albumin across primary human microvascular endothelial cells from both lung and skin. We then validated our in vitro findings using a tissue-specific knockout mouse model. We observed that albumin transcytosis was saturable in the skin but not the lung microvascular endothelial cells, implicating a receptor-mediated process...
January 31, 2019: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://read.qxmd.com/read/30675804/local-pulmonary-drug-delivery-in-the-preterm-rabbit-feasibility-and-efficacy-of-daily-intratracheal-injections
#17
Thomas Salaets, Andre Gie, Julio Jimenez, Margo Aertgeerts, Olivier Gheysens, Greetje Vande Velde, Michel Koole, Xabi Murgia, Costanza Casiraghi, Francesca Ricci, Fabrizio Salomone, Gino Villetti, Karel Allegaert, Jan Deprest, Jaan Toelen
Recent clinical trials in newborns have successfully used surfactant as a drug carrier for an active compound, in order to minimize systemic exposure. To investigate the translational potential of surfactant-compound mixtures and other local therapeutics, a relevant animal model is required where intratracheal (IT) administration for maximal local deposition is technically possible and well tolerated. Preterm rabbit pups (born at 28 days of gestation) were exposed to either hyperoxia or normoxia and randomized to receive daily IT surfactant, daily IT saline or no injections for 7 days...
January 24, 2019: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://read.qxmd.com/read/30675803/impact-of-aging-on-inflammatory-and-immune-responses-during-elastin-peptide-induced-murine-emphysema
#18
Alexandre Pierre, Flora Lemaire, Aïda Meghraoui-Kheddar, Sandra Audonnet, Stéphanie Héry-Huynh, Richard Le Naour
Deterioration of lung functions and degradation of elastin fibers with age are accelerated during chronic obstructive pulmonary disease (COPD). Excessive genesis of soluble elastin peptides (EP) is a key factor in the pathophysiology of COPD. We have previously demonstrated that 6-week old mice exhibited emphysematous structural changes associated with pro-inflammatory immune response after EP instillation. In this study, we investigated the consequences of aging on inflammatory, immune and histological criteria associated with murine emphysema progression after EP exposure...
January 24, 2019: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://read.qxmd.com/read/30675802/the-tcf21-lineage-constitutes-the-lung-lipofibroblast-population
#19
Juwon Park, Malina J Ivey, Yanik Deana, Kara Riggsbee, Emelie Sörensen, Veronika Schwabl, Caroline Sjöberg, Tilda Hjertberg, Ga Young Park, Jessica M Swonger, Taylor Rosengreen, Rory E Morty, Katrin Ahlbrecht, Michelle Diane Tallquist
Transcription factor 21 (Tcf21) is a bHLH transcription factor required for mesenchymal development in several organs. Others have demonstrated that Tcf21 is expressed in embryonic lung mesenchyme and that loss of Tcf21 results in a pulmonary hypoplasia phenotype. Although recent single-cell transcriptome analysis has described multiple mesenchymal cell types in the lung, few have characterized the Tcf21 expressing population. To explore the Tcf21 mesenchymal lineage, we traced Tcf21 expressing cells during embryogenesis and in the adult...
January 24, 2019: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://read.qxmd.com/read/30652497/inhibition-of-ggpps1-attenuated-lps-induced-acute-lung-injury-and-was-associated-with-nlrp3-inflammasome-suppression
#20
Wujian Xu, Xiaoxia Wang, Jiajia Jin, Qian Zou, Lin Wu, Tangfeng Lv, Bing Wan, Ping Zhan, Suhua Zhu, Hongbing Liu, Ningwei Zhao, Chaojun Li, Yong Song
Inhibition of the mevalonate pathway using statins has been shown to be beneficial in the treatment of acute lung injury (ALI). Here, we investigated whether partial inhibition of this pathway by targeting Geranylgeranyl pyrophosphate synthase large subunit 1 (GGPPS1), a catalase downstream of the mevalonate pathway, was effective at treating lung inflammation in ALI. Lipopolysaccharide (LPS) was intra-tracheally instilled to induce ALI in lung specific GGPPS1 knockout and wild-type mice. Expression of GGPPS1 in lung tissues and alveolar epithelial cells was examined...
January 17, 2019: American Journal of Physiology. Lung Cellular and Molecular Physiology
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