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American Journal of Physiology. Lung Cellular and Molecular Physiology

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https://www.readbyqxmd.com/read/30234377/connexin-40-regulates-lung-endothelial-permeability-in-acute-lung-injury-via-the-rock1-mypt1-mlc20-pathway
#1
Jun Yin, Lu Lv, Peng Zhai, Tao Long, Qiang Zhou, Huiwen Pan, Godwin Botwe, Liming Wang, Qun Wang, Lijie Tan, Wolfgang Michael Kuebler
Increased pulmonary vascular permeability is a hallmark of acute lung injury (ALI). Connexin 40 (Cx40) is a gap junctional protein abundantly present in the lung microvascular endothelium. Yet, the role of Cx40 in the regulation of lung vascular permeability and its underlying mechanisms are unclear. Here, we tested the hypothesis that Cx40 participates in regulation of lung endothelial permeability via a mechanism involving a Rho-associated protein kinase (ROCK) dependent regulation of myosin light chain (MLC)...
September 20, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/30234376/hypoxia-inhibits-adenylyl-cyclase-catalytic-activity-in-a-porcine-model-of-persistent-pulmonary-hypertension-of-the-newborn
#2
Anurag Singh Sikarwar, Martha Hinton, Kallivalappil Thomas Santhosh, Premnath Dhanaraj, Mariel Talabis, Prashen Chelikani, Shyamala Dakshinamurti
OBJECTIVE: Persistent pulmonary hypertension of the newborn (PPHN) features hypoxemia, pulmonary vasoconstriction and impaired cardiac inotropy. We reported low basal and stimulated cAMP in hypoxic pulmonary artery smooth muscle cells (PASMC). We now examine pulmonary arterial adenylyl cyclase (AC) activity and regulation in hypoxic PPHN. APPROACH: PPHN was induced in newborn swine by normobaric hypoxia (FiO2 0.10) for 72hr; age-matched normoxic controls. We studied relaxation of pulmonary arterial rings to AC activator forskolin and sGC activator sodium nitroprusside (SNP) by isometric myography; ATP content, phosphodiesterase activity, AC content, isoform expression and catalytic activity in presence or absence of Gαs-coupled receptor agonists, forskolin, or trans-nitrosylating agents, in human and neonatal porcine PASMC, and HEK293T stably expressing AC isoform 6, after 72 hour hypoxia (10% O2) or normoxia (21% O2)...
September 20, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/30234375/spontaneous-pulmonary-hypertension-in-genetic-mouse-models-of-natural-killer-cell-deficiency
#3
Matthew T Ratsep, Stephen D Moore, Salema Jafri, Melissa Mitchell, Hugh Jm Brady, Ofer Mandelboim, Mark Southwood, Nicholas W Morrell, Francesco Colucci, Mark L Ormiston
Natural Killer (NK) cells are cytotoxic innate lymphoid cells with an established role in the regulation of vascular structure in pregnancy and cancer. Impaired NK cell function has been identified in patients with pulmonary arterial hypertension (PAH), a disease of obstructive vascular remodeling in the lungs, as well as in multiple rodent models of disease. However, the precise contribution of NK cell impairment to the initiation and progression of PAH remains unknown. Here we report the development of spontaneous pulmonary hypertension in two independent genetic models of NK cell dysfunction, including Nfil3-/- mice, which are deficient in NK cells due to the absence of the NFIL3 transcription factor, and Ncr1-Gfp mice, which lack the NK activating receptor NKp46...
September 20, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/30211655/former-preterm-lambs-have-persistent-alveolar-simplification-at-2-and-5-months-corrected-postnatal-age
#4
Mar Janna Dahl, Sydney Bowen, Toshio Aoki, Andrew Rebentisch, Elaine Dawson, Luke Pettet, Haleigh Emerson, Baifeng Yu, Zheng-Ming Wang, Haixia Yang, Chong Zhang, Angela P Presson, Lisa A Joss-Moore, Donald M Null, Bradley A Yoder, Kurt H Albertine
Preterm birth and mechanical ventilation (MV) frequently lead to bronchopulmonary dysplasia, the histopathological hallmark of which is alveolar simplification. How developmental immaturity and ongoing injury, repair, and remodeling impact completion of alveolar formation later in life is not known, in part because of lack of suitable animal models. We report a new model using former preterm lambs to test the hypothesis that they will have persistent alveolar simplification later in life. Moderately preterm lambs (~85% gestation) were supported by MV for ~6 days before being transitioned from all respiratory support to become former preterm lambs...
September 13, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/30211654/oxidative-stress-associated-with-aging-activates-protein-kinase-c-epsilon-leading-to-cilia-slowing
#5
Kristina L Bailey, Kusum K Kharbanda, Dawn M Katafiasz, Joseph H Sisson, Todd A Wyatt
Older people are four times more likely to develop pneumonia than younger people. As we age, many components of pulmonary innate immunity are impaired, including slowing of mucociliary clearance. Ciliary beat frequency (CBF) is a major determinant of mucociliary clearance, and it slows as we age. We hypothesized that CBF is slowed in aging due to increased oxidative stress, which activates PKCε signaling. We pharmacologically inhibited PKCε in ex vivo mouse models of aging. We measured a slowing of CBF with aging that was reversed with inhibition using the novel PKC inhibitor, Ro-31-8220, as well as the PKCε inhibitor, PKCe141...
September 13, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/30211653/generation-of-an-alveolar-epithelial-type-ii-cell-line-from-induced-pluripotent-stem-cells
#6
Luca Tamo, Youssef Hibaoui, Sampada Kallol, Marco P Alves, Christiane Albrecht, Katrin E Hostettler, Anis Feki, Jean-Sebastien Rougier, Hugues Abriel, Lars Knudsen, Amiq Gazdhar, Thomas Geiser
Differentiation of primary alveolar type II epithelial cells (AEC type II) to AEC type I in culture is a major barrier in the study of the alveolar epithelium in vitro. The establishment of an AEC type II cell line derived from induced pluripotent stem cells (iPSC) represents a novel opportunity to study alveolar epithelial cell biology, for instance in the context of lung injury, fibrosis and repair. In the present study, we generated long lasting AECII from iPSC (iPSC-AEC). Long lasting iPSC-AECII (LL)-iPSC-AECII) displayed morphological characteristics of AECII including growth in a cobble stone monolayer, the presence of lamellar bodies and microvilli as shown by electron microscopy...
September 13, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/30211652/buffer-drains-and-mucus-is-transported-upward-in-a-tilted-mucus-clearance-assay
#7
Jerome Carpenter, Suzanne E Lynch, Jeremy A Cribb, Schuyler Kylstra, David B Hill, Richard Superfine
Mucociliary clearance (MCC) plays an essential role in maintaining airway sterility and health. Conversely, mucociliary dysfunction is implicated across many airway obstructive diseases. Understanding the necessary requirements for successful MCC is imperative to establish the pathology of disease as well as to develop therapeutic strategies. Although gravitational drainage is used clinically via postural drainage to aid mucus clearance, it is ignored in both animal and cell culture models of MCC. In this study we develop a novel mucus clearance assay that enables the first particle image velocimetry of human bronchial epithelial cell cultures tilted relative to the gravitational field...
September 13, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/30211651/pdgfbb-promotes-proliferation-and-migration-via-regulating-mir-1181-stat3-axis-in-human-pulmonary-arterial-smooth-muscle-cells
#8
Zhengjiang Qian, Yanjiao Li, Haiyang Yang, Jidong Chen, Xiang Li, Deming Gou
Platelet-Derived Growth Factor (PDGF) can induce hyperproliferation of Pulmonary Artery Smooth Muscle Cells (PASMCs), which is a key causative factor to the occurrence and progression of pulmonary arterial hypertension (PAH). We previously identified that miR-1181 is significantly downregulated by PDGFBB in human PASMCs. In this work, we further explore the function of miR-1181 and underlying regulatory mechanisms in PDGF-induced PASMCs. First, the expression pattern of miR-1181 was characterized under PDGFBB treatment, and PDGFR/PKCβ signaling was find to repress miR-1181 expression...
September 13, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/30188748/mitochondrial-peptides-cause-proinflammatory-responses-in-the-alveolar-epithelium-via-fpr-1-mapks-and-akt-a-potential-mechanism-involved-in-acute-lung-injury
#9
Xue Zhang, Tao Wang, Zhi-Cheng Yuan, Lu-Qi Dai, Ni Zeng, Hao Wang, Lian Liu, Fu-Qiang Wen
Acute lung injury (ALI) is characterized by alveolar epithelial damage and uncontrolled pulmonary inflammation. Mitochondrial damage-associated molecular patterns (DAMPs), including mitochondrial peptides (N-formyl peptides, NFPs), are released during cell injury and death and induce inflammation by unclear mechanisms. In this study, we have investigated the role of mitochondrial DAMPs (MTDs), especially NFPs, in alveolar epithelial injury and lung inflammation. In murine models of ALI, high levels of mitochondrial NADH dehydrogenase 1 in bronchoalveolar lavage fluid (BALF) were associated with lung injury scores and increased formyl peptide receptor (FPR)-1 expression in the alveolar epithelium...
September 6, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/30188747/interaction-between-the-retrotrapezoid-nucleus-and-the-parafacial-respiratory-group-to-regulate-active-expiration-and-sympathetic-activity-in-rats
#10
Daniel B Zoccal, Josiane N Silva, William H Barnett, Eduardo V Lemes, Barbara Falquetto, Eduardo Colombari, Yaroslav I Molkov, Thiago S Moreira, Ana C Takakura
The retrotrapezoid nucleus (RTN) contains chemosensitive cells that distribute CO2-dependent excitatory drive to the respiratory network. This drive facilitates the function of the respiratory central pattern generator (rCPG) and increases sympathetic activity. It is also evidenced that during hypercapnia, the late-expiratory (late-E) oscillator in the parafacial respiratory group (pFRG) is activated and determine the emergence of active expiration. However, it remains unclear the microcircuitry responsible for the distribution of the excitatory signals to the pFRG and the rCPG in conditions of high CO2...
September 6, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/30188746/high-molecular-weight-hyaluronan-ameliorates-allergic-inflammation-and-airway-hyperresponsiveness-in-the-mouse
#11
Collin G Johnson, Vandy P Stober, Jaime M Cyphert-Daly, Carol S Trempus, Gordon P Flake, Valbona Cali, Israr Ahmad, Ronald J Midura, Mark A Aronica, Sadis Matalon, Stavros Garantziotis
Allergic asthma is a major cause of morbidity in both pediatric and adult patients. Recent research has highlighted the role of hyaluronan, an extracellular matrix glycosaminoglycan, in asthma pathogenesis. Experimental allergic airway inflammation and clinical asthma are associated with an increase of shorter fragments of hyaluronan (sHA), which complex with inter-α-inhibitor heavy chains (HC) and induce inflammation and airway hyperresponsiveness (AHR). Importantly, the effects of sHA can be antagonized by the physiological counterpart high-molecular-weight hyaluronan (HMWHA)...
September 6, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/30188745/dpp4-inhibition-by-sitagliptin-attenuates-lps-induced-lung-injury-in-mice
#12
Takeshi Kawasaki, Weiguo Chen, Yu Maw Htwe, Koichiro Tatsumi, Steven M Dudek
Acute respiratory distress syndrome (ARDS) is a severe clinical condition marked by acute respiratory failure and dysregulated inflammation. Pulmonary vascular endothelial cells (PVEC) function as an important pro-inflammatory source in ARDS, suggesting that modulation of inflammatory events at the endothelial level may have therapeutic benefit. Dipeptidyl peptidase-4 (DPP4) inhibitors, widely used for the treatment of diabetes mellitus, have been reported to have possible anti-inflammatory effects. However, the potential anti-inflammatory effects of DPP4 inhibition on PVEC function and ARDS pathophysiology are unknown...
September 6, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/30160518/obesity-increases-airway-smooth-muscle-responses-to-contractile-agonists
#13
Sarah Orfanos, Joseph Jude, Brian Thomas Deeney, Gaoyuan Cao, Deepa Rastogi, Mark van Zee, Ivan Pushkarsky, Hector E Munoz, Robert Damoiseaux, Dino Di Carlo, Reynold Panettieri
BACKGROUND: The asthma-obesity syndrome represents a major public health concern that disproportionately contributes to asthma severity and induces insensitivity to therapy. To date, no study has shown an intrinsic difference between human airway smooth muscle (HASM) cells derived from non-obese subjects and those derived from obese subjects. The objective of this study was to address whether there is a greater response to agonist-induced calcium mobilization, phosphorylation of myosin light chain (MLC) and greater shortening in HASM cells derived from obese subjects...
August 30, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/30136611/hiv-transgene-expression-impairs-k-channel-function-in-the-pulmonary-vasculature
#14
Gema Mondejar-Parreño, Daniel Morales-Cano, Bianca Barreira, Maria Callejo, Jesus Ruiz-Cabello, Laura Moreno, Sergio Esquivel-Ruiz, Alistair Mathie, Ghazwan Butrous, Francisco Perez-Vizcaino, Angel Cogolludo
Human immunodeficiency virus (HIV) infection is an established risk factor for pulmonary arterial hypertension (PAH), however the pathogenesis of HIV-related PAH remains unclear. Since K+ channel dysfunction is a common marker in most forms of PAH, our aim was to analyse if the expression of HIV proteins is associated with impairment of K+ channel function in the pulmonary vascular bed. HIV transgenic mice (Tg26) expressing seven of the nine HIV viral proteins and wild type (Wt) mice were used. Hemodynamic assessment was performed by echocardiography and catheterization...
August 23, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/30136610/potentiation-of-the-cystic-fibrosis-transmembrane-conductance-regulator-cl-channel-by-ivacaftor-is-temperature-independent
#15
Yiting Wang, Zhiwei Cai, Martin Gosling, David N Sheppard
Ivacaftor is the first drug to target directly defects in the cystic fibrosis transmembrane conductance regulator (CFTR), which cause cystic fibrosis (CF). To understand better how ivacaftor potentiates CFTR channel gating, here we investigated the effects of temperature on its action. As a control, we studied the benzimidazolone UCCF -853, which potentiates CFTR by a different mechanism. Using the patch-clamp technique and cells expressing recombinant CFTR, we studied the single-channel behavior of wild-type and F508del-CFTR, the most common CF mutation...
August 23, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/30136609/inhibition-of-the-extrinsic-or-intrinsic-coagulation-pathway-during-pneumonia-derived-sepsis
#16
Ingrid Stroo, Chao Ding, Andreja Novak, Jack Yang, Joris J T H Roelofs, Joost C M Meijers, Alexey Revenko, Cornelis van 't Veer, Sacha Zeerleder, Jeff R Crosby, Tom van der Poll
Pneumonia is the most frequent cause of sepsis and Klebsiella (K.) pneumoniae is a common pathogen in pneumonia and sepsis. Infection is associated with activation of the coagulation system. Coagulation can be activated by the extrinsic and intrinsic routes, mediated by factor (F) VII and FXII respectively. To determine the role of FVII and FXII in the host response during pneumonia derived sepsis, mice were treated with specific antisense oligonucleotide (ASO) directed at FVII or FXII for three weeks prior to infection with K...
August 23, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/30113229/umbilical-cord-blood-metabolomics-reveal-distinct-signatures-of-dyslipidemia-prior-to-bronchopulmonary-dysplasia-and-pulmonary-hypertension
#17
Michael La Frano, Johannes Fahrmann, Dmitry Grapov, Theresa Pedersen, John W Newman, Oliver Fiehn, Mark A Underwood, Karen K Mestan, Robin Steinhorn, Stephen Wedgwood
Pulmonary hypertension (PH) is a common consequence of bronchopulmonary dysplasia (BPD) and remains a primary contributor to increased morbidity and mortality among preterm infants. Unfortunately, at the present time there are no reliable early predictive markers for BPD-associated PH. Considering its health consequences, understanding in utero perturbations that lead to the development of BPD and BPD-associated PH and identifying early predictive markers is of utmost importance. As part of the discovery phase, we applied a multi-platform metabolomics approach consisting of untargeted and targeted methodologies to screen for metabolic perturbations in umbilical cord blood (UCB) plasma from preterm infants that did (n=21; cases) or did not (n=21; controls) develop subsequent PH...
August 16, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/30113228/ancestry-and-genetic-associations-with-bronchopulmonary-dysplasia-in-preterm-infants
#18
Dara G Torgerson, Philip Ballard, Roberta L Keller, Sam Oh, Scott Huntsman, Donglei Hu, Celeste Eng, Esteban Burchard, Roberta Ballard, The Tolsurf Study Group
Bronchopulmonary dysplasia in premature infants is a common and often severe lung disease with long term sequelae. A genetic component is suspected but not fully defined. We performed an ancestry and genome-wide association study to identify variants, genes and pathways associated with survival without bronchopulmonary dysplasia in 387 high-risk infants treated with inhaled nitric oxide in the Trial of Late Surfactant study. Global African genetic ancestry was associated with increased survival without bronchopulmonary dysplasia among infants of maternal self-reported Hispanic White race/ethnicity (OR=4...
August 16, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/30113227/early-airway-microbial-metagenomic-and-metabolomic-signatures-are-associated-with-development-of-severe-bronchopulmonary-dysplasia
#19
Charitharth Vivek Lal, Jegen Kandasamy, Kalsang Dolma, Manimaran Ramani, Ranjit Kumar, Landon Wilson, Zubair H Aghai, Stephen Barnes, J Edwin Blalock, Amit Gaggar, Vineet Bhandari, Namasivayam Ambalavanan
The pathogenesis of bronchopulmonary dysplasia (BPD) is not well understood. We previously identified differences in the airway microbiome at birth between preterm infants who were BPD-predisposed versus those who were BPD-resistant. In this study, we attempted to identify mechanisms by which the airway microbiome could modify the risk for BPD. We used a software-based method to predict the metagenome of the tracheal aspirate (TA) microbiome from 16s rRNA sequencing data in preterm infants and to identify functional ortholog genes that were differentially abundant in BPD-predisposed and BPD-resistant infants...
August 16, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/30091382/macrophages-from-the-upper-and-lower-human-respiratory-tract-are-metabolically-distinct
#20
Katelyn S Lavrich, Adam M Speen, Andrew J Ghio, Philip A Bromberg, James M Samet, Neil E Alexis
The function and cell surface phenotype of lung macrophages vary within the respiratory tract. Whether the bioenergetic profile of macrophages also differs depending on location within the lung is currently unknown. This study sought to characterize the bioenergetic profile of macrophages sampled from different locations within the respiratory tract at baseline and in response to ex vivo xenobiotic challenge. Surface macrophages recovered from healthy volunteers by induced sputum and by bronchial and bronchoalveolar lavage were profiled using extracellular flux analyses...
August 9, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
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