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American Journal of Respiratory Cell and Molecular Biology

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https://www.readbyqxmd.com/read/28107636/visceral-white-adipose-tissue-following-chronic-intermittent-and-sustained-hypoxia-in-mice
#1
David Gozal, Alex Gileles-Hillel, Rene Cortese, Yan Li, Isaac Almendros, Zhuanhong Qiao, Ahamed A Khalyfa, Jorge Andrade, Abdelnaby Khalyfa
BACKGROUND: Angiogenesis, a process induced by hypoxia in visceral white adipose tissue (vWAT) in the context of obesity, mediates obesity-induced metabolic dysfunction and insulin resistance. Chronic intermittent hypoxia (IH) and sustained hypoxia (SH) induce body weight reductions and insulin resistance of differing magnitude, suggesting different HIF-1α-related activity. METHODS: 8-week old male C57BL/6J mice (n=10-12/group) were exposed to either IH, SH,or room air (RA)...
January 20, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28085510/age-dependent-changes-of-ampk-metabolic-pathways-in-the-lung-in-a-mouse-model-of-hemorrhagic-shock
#2
Lindsey R Klingbeil, Paul Kim, Giovanna Piraino, Michael O'Connor, Paul W Hake, Vivian Wolfe, Basilia Zingarelli
RATIONALE: The development of multiple organ failure in patients with hemorrhagic shock is significantly impacted by the patient age. AMP-activated protein kinase (AMPK) is a crucial regulator of energy homeostasis, which coordinates metabolic repair during cellular stress. OBJECTIVES: We investigated whether AMPK-regulated signaling pathways are age-dependent in hemorrhage-induced lung injury and whether AMPK activation by 5-amino-4-imidazole carboxamide riboside (AICAR) affords lung protective effects...
January 13, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28085498/mouse-genome-wide-association-study-of-pre-clinical-group-ii-pulmonary-hypertension-identifies-egfr
#3
Neil J Kelly, Josiah E Radder, Jeffrey J Baust, Christine L Burton, Yen-Chun Lai, Karin C Potoka, Brittani A Agostini, John P Wood, Timothy N Bachman, Rebecca R Vanderpool, Nadine Dandachi, Adriana S Leme, Alyssa D Gregory, Alison Morris, Ana L Mora, Mark T Gladwin, Steven D Shapiro
RATIONALE: Pulmonary hypertension (PH) is associated with features of obesity and metabolic syndrome that translate to the induction of PH by chronic high-fat diet (HFD) in some inbred mouse strains. We conducted a genome-wide association study (GWAS) to identify candidate genes associated with susceptibility to HFD-induced PH. METHODS: Mice from 36 inbred and wild-derived strains were fed with regular diet (RD) or HFD for 20 weeks beginning at 6-12 weeks of age after which right ventricular (RV) and left ventricular (LV) end-systolic pressure (ESP) and maximum pressure (MaxP) were measured by cardiac catheterization...
January 13, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28085493/metabolism-and-skeletal-muscle-homeostasis-in-lung-disease
#4
Ermelinda Ceco, Samuel E Weinberg, Navdeep S Chandel, Jacob I Sznajder
There is increased awareness that patients with lung diseases develop muscle dysfunction. Muscle dysfunction is a major contributor to a decreased quality of life in patients with chronic pulmonary diseases. Furthermore, muscle dysfunction exacerbates lung disease outcome, as a decrease in muscle mass and function are associated with increased morbidity, often long after critical illness or lung disease has been resolved. As we are learning more about the role of metabolism in health and disease, we are appreciating more the direct role of metabolism in skeletal muscle homeostasis...
January 13, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28080134/alveolar-epithelial-cell-derived-mediators-potential-direct-regulators-of-large-airway-and-vascular-responses
#5
Elizabeth A Oczypok, Timothy N Perkins, Tim D Oury
Bronchial epithelial cells and pulmonary endothelial cells are thought to be the primary modulators of conducting airways and vessels, respectively. However, histological examination of both mouse and human lung tissue reveals that alveolar epithelial cells (AECs) line the adventitia of large airways and vessels and thus are also in a position to directly regulate these structures. The primary purpose of this perspective is to highlight that AECs coat the adventitial surface of every vessel and airway in the lung parenchyma...
January 12, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28060543/inhibition-of-the-kca3-1-channel-alleviates-established-pulmonary-fibrosis-in-a-large-animal-model
#6
Louise Organ, Barbara Bacci, Emmanuel Koumoundouros, Wayne G Kimpton, Chrishan S Samuel, Cameron J Nowell, Peter Bradding, Katy M Roach, Glen Westall, Jade Jaffar, Ken J Snibson
Idiopathic pulmonary fibrosis is a chronic progressive disease of increasing prevalence marked by poor prognosis and limited treatment options. Ca2+-activated KCa3.1 potassium channels have been shown to play a key role in the aberrant activation and responses to injury in both epithelial cells and fibroblasts, both considered key drivers in the fibrotic process of IPF. Pharmacological inhibition of IPF-derived fibroblasts is able to somewhat prevent TGF-βand bFGF-dependent profibrotic responses. In the current study, we investigated whether blockade of the KCa3...
January 6, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28059551/wnt-signaling-in-chronic-rhinosinusitis-with-nasal-polyps
#7
Robert Böscke, Eszter K Vladar, Michael Könnecke, Birgit Hüsing, Robert Linke, Ralph Pries, Norbert Reiling, Jeffrey D Axelrod, Jayakar V Nayak, Barbara Wollenberg
The signaling pathways that sustain the disease process of chronic rhinosinusitis with nasal polyps (CRSwNP) remain poorly understood. We sought to determine the expression levels of Wnt signaling genes in CRSwNP, and to study the role of the Wnt pathway in inflammation and epithelial remodeling in the nasal mucosa. Microarrays and RT-qPCR comparing gene expression in matched nasal polyps (NP) and inferior turbinates (IT) revealed that WNT2B, WNT3A, WNT4, WNT7A, WNT7B and FZD2 were upregulated, and FZD1, LRP5, LRP6 and WIF1 downregulated in NPs...
January 6, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28005397/tns1-is-essential-for-myofibroblast-differentiation-and-extracellular-matrix-formation
#8
Ksenija Bernau, Elizabeth E Torr, Michael D Evans, Jason K Aoki, Caitlyn R Ngam, Nathan Sandbo
Myofibroblasts, the primary effector cells that mediate matrix remodeling during pulmonary fibrosis, rapidly assemble an extracellular fibronectin matrix1. Tensin1 (TNS1) is a key component of specialized cellular adhesions (fibrillar adhesions) that bind to extracellular fibronectin fibrils. We hypothesized that TNS1 may play a role in modulating myofibroblast-mediated matrix formation. We found that TNS1 expression is increased in fibroblastic foci from lungs with idiopathic pulmonary fibrosis. TGF-β profoundly upregulates TNS1 expression with kinetics that parallel the expression of the myofibroblast marker, ACTA2...
December 22, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27997810/glut-1-dependent-glycolysis-is-increased-during-aging-related-lung-fibrosis-and-phloretin-inhibits-lung-fibrosis
#9
Soo Jung Cho, Jong-Seok Moon, Chang-Min Lee, Augustine M K Choi, Heather W Stout-Delgado
RATIONAL: Aging is associated with metabolic diseases such as type 2 diabetes mellitus, cardiovascular disease, cancer and neurodegeneration. Aging contributes to common processes including metabolic dysfunction, DNA damage and reactive oxygen species generation. While glycolysis has been linked to cell growth and proliferation, the mechanisms by which the activation of glycolysis by aging regulates fibrogenesis in lung remain unclear. OBJECTIVES: To determine if glucose transport 1 (GLUT1)-induced glycolysis regulates age-dependent fibrogenesis of the lung...
December 20, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27997807/roflumilast-n-oxide-in-combination-with-formoterol-enhances-the-anti-inflammatory-effect-of-dexamethasone-in-asm-cells
#10
Brijeshkumar S Patel, Md Mostafizur Rahman, Gina Baehring, Dikaia Xenaki, Francesca Su-May Tang, Brian G Oliver, Alaina J Ammit
Roflumilast is an orally active phosphodiesterase 4 (PDE4) inhibitor approved for use in chronic obstructive pulmonary disease. Roflumilast N-oxide (RNO) is the active metabolite of roflumilast and has demonstrated anti-inflammatory impact in vivo and in vitro. To date, the effect of RNO on the synthetic function of airway smooth muscle (ASM) cells is unknown. We address this herein and investigate the effect of RNO on β2-adrenoceptor-mediated, cAMP-dependent responses in ASM cells in vitro, and whether RNO enhances steroid-induced repression of inflammation...
December 20, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27983869/pharmacological-rescue-of-conditionally-reprogrammed-cystic-fibrosis-bronchial-epithelial-cells
#11
Martina Gentzsch, Susan E Boyles, Chaitra Cheluvaraju, Imron G Chaudhry, Nancy L Quinney, Crescentia Cho, Hong Dang, Xuefeng Liu, Richard Schlegel, Scott H Randell
Well-differentiated primary human bronchial epithelial (HBE) cell cultures are vital for cystic fibrosis (CF) research, particularly for development of CF transmembrane conductance regulator (CFTR) modifier drugs. Culture of epithelial cells with irradiated 3T3 fibroblast feeder cells plus the RhoA kinase (ROCK) inhibitor Y-27632 (Y), termed conditionally reprogrammed cell (CRC) technology, enhances cell growth and lifespan while preserving cell of origin functionality. We initially determined the electrophysiological and morphological characteristics of conventional versus CRC expanded non-CF HBE cells...
December 16, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27977296/phosphoinositide-3-kinase-in-asthma-novel-roles-and-therapeutic-approaches
#12
Edwin J Yoo, Christie A Ojiaku, Krishna Sunder, Reynold A Panettieri
Asthma manifests as airway hyperresponsiveness and inflammation, including coughing, wheezing, and shortness of breath. Immune cells and airway structural cells orchestrate asthma pathophysiology, leading to mucus secretion, airway narrowing, and obstruction. Phosphoinositide 3-kinase (PI3K), a lipid kinase, plays a crucial role in many of the cellular and molecular mechanisms driving asthma pathophysiology, and represents an attractive therapeutic target. Here, we summarize the diverse roles of PI3K in the pathogenesis of asthma and discuss novel therapeutic approaches to treatment...
December 15, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27967234/alternative-progenitor-lineages-regenerate-the-adult-lung-depleted-of-type-ii-cells
#13
Min Yee, William Domm, Robert Gelein, Karen L de Mesy Bentley, R Matthew Kottmann, Patricia J Sime, B Paige Lawrence, Michael A O'Reilly
An aberrant oxygen environment at birth increases the severity of respiratory viral infections later in life through poorly understood mechanisms. Here we show that alveolar epithelial type II (AEC2) cells, a progenitor for AEC1 cells are depleted in adult mice exposed to neonatal hypoxia or hyperoxia. Airway cells expressing SP-C and ABCA3, alveolar pod cells expressing KRT5, and pulmonary fibrosis was observed when these mice were infected with a sublethal dose of HKx31, H3N2 influenza A virus (IAV). This was not seen in infected siblings birthed into room air...
December 14, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27922761/%C3%AE-6%C3%AE-4-integrin-regulates-the-collective-migration-of-epithelial-cells
#14
Zachary T Colburn, Jonathan C R Jones
α6β4 integrin is localized in a unique punctate distribution at the cell-substratum interface along the leading front of single, front-rear polarized, A549 cells. These puncta are interspersed between focal adhesions and lack association with the actin cytoskeleton. Knockdown of β4 integrin in A549 cells inhibits their directed migration, with knockdown cells exhibiting large focal adhesions and reduced actin dynamics. Despite these changes, the speed of knockdown cells is equivalent to controls cells. Interestingly, in such cells, α6 integrin retains its punctate distribution...
December 6, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27911588/pulmonary-innate-immune-dysfunction-in-hiv
#15
Bashar S Staitieh, Eduardo E Egea, David M Guidot
The advent of anti-retroviral therapy (ART) has transformed infection by the type 1 human immunodeficiency virus (HIV) from a rapidly fatal disease to a chronic illness with excellent long-term survival rates. Although HIV primarily targets the adaptive arm of host immunity, it simultaneously impacts the innate immune system and has profound implications for lung health even when viral suppression is achieved with ART. The lung has evolved a unique array of innate immune defenses and the pathophysiological interactions between HIV and the pulmonary innate immune system deserve particular attention...
December 2, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27911568/nf%C3%AE%C2%BAb-mediates-mesenchymal-transition-remodeling-and-pulmonary-fibrosis-in-response-to-chronic-inflammation-by-viral-rna-patterns
#16
Bing Tian, Igor Patrikeev, Lorenzo Ochoa, Gracie Vargas, KarryAnne K Belanger, Julia Litvinov, Istvan Boldogh, Bill T Ameredes, Massoud Motamedi, Allan R Brasier
Airway remodeling is resultant of a complex multi-cellular response associated with a progressive decline of pulmonary function in patients with chronic airway disease. Here, repeated infections with respiratory viruses are linked with airway remodeling through largely unknown mechanisms. Although acute activation of the Toll like receptor (TLR)3 pathway by extracellular poly(I:C) induces innate signaling through the NFkB transcription factor in human small airway epithelial cells (hSAECs), prolonged (repetitive or tonic) poly(I:C) stimulation produces chronic stress fiber formation, mesenchymal transition and activation of a fibrotic program...
December 2, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27875656/involvement-of-jnk-in-tnf%C3%AE-driven-remodelling
#17
Irene Mj Eurlings, Niki L Reynaert, Cheryl van de Wetering, Scott W Aesif, Evi M Mercken, Rafael de Cabo, Jos L van der Velden, Yvonne M Janssen-Heininger, Emiel F M Wouters, Mieke A Dentener
Lung tissue remodeling in chronic obstructive pulmonary disease (COPD) is characterized by airway wall thickening and/or emphysema. Although the bronchial and alveolar compartments are functionally independent entities, we recently showed comparable alterations in matrix composition comprised of decreased elastin content and increased collagen and hyaluronan contents of alveolar and small airway walls. Out of several animal models tested SPC-TNFα mice showed remodelling in alveolar and airway walls similar to what is observed in COPD patients...
November 22, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27870560/effect-of-prenatal-versus-postnatal-vitamin-d-deficiency-on-pulmonary-structure-and-function-in-mice
#18
Ammar Saadoon, Namasivayam Ambalavanan, Kurt Zinn, Ambika P Ashraf, Mark MacEwen, Teodora Nicola, Michelle V Fanucchi, William T Harris
Epidemiologic studies have linked gestational vitamin D deficiency to respiratory diseases, although mechanisms have not been defined. We hypothesized that antenatal vitamin D deficiency would impair airway development and alveolarization in a mouse model. We studied the effect of antenatal vitamin D deficiency by inducing vitamin D deficiency in pregnant mice and then compared lung development and function in their offspring to littermate controls. Postnatal vitamin D deficiency and sufficiency models from each group were also studied...
November 21, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27854516/evasion-of-neutrophil-extracellular-traps-by-respiratory-pathogens
#19
Daniel M L Storisteanu, Joanna M Pocock, Andrew S Cowburn, Jatinder K Juss, Angalee Nadesalingam, Victor Nizet, Edwin R Chilvers
The release of neutrophil extracellular traps (NETs) is a major immune mechanism intended to capture pathogens. These histone and protease-coated DNA structures are released by neutrophils in response to a variety of stimuli, including respiratory pathogens, and have been identified in the airways of patients with respiratory infection, cystic fibrosis, acute lung injury, primary graft dysfunction and COPD. NET production has been demonstrated in the lungs of mice infected with Staphylococcus aureus, Klebsiella pneumoniae and Aspergillus fumigatus...
November 17, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27854509/tgf-%C3%A3-1-function-in-airway-remodeling-and-hyperresponsiveness-the-missing-link
#20
Christie A Ojiaku, Edwin J Yoo, Reynold A Panettieri
The pathogenesis of asthma includes a complex interplay between airway inflammation, hyperresponsiveness, and remodeling. Current evidence suggests that airway structural cells - including bronchial smooth muscle cells, myofibroblasts, fibroblasts, and epithelial cells -mediate all three aspects of asthma pathogenesis. While studies show a connection between airway remodeling and changes in bronchomotor tone, the relationship between the two remains unclear. Transforming growth factor beta 1 (TGF-ß1), a growth factor elevated in the airway of patients with asthma, plays a role in airway remodeling and the shortening of various airway structural cells...
November 17, 2016: American Journal of Respiratory Cell and Molecular Biology
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