5,246 results match your criteria American Journal of Physiology - Lung Cellular and Molecular Physiology[Journal]


Bringing the Cellular Clock into Understanding Lung Disease: It's Time, Period!

Am J Physiol Lung Cell Mol Physiol 2020 Jul 8. Epub 2020 Jul 8.

Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, United States.

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http://dx.doi.org/10.1152/ajplung.00320.2020DOI Listing

Transcriptomic Modifications in Developmental Cardiopulmonary Adaptations to Chronic Hypoxia Using a Murine Model of Simulated High Altitude Exposure.

Am J Physiol Lung Cell Mol Physiol 2020 Jul 8. Epub 2020 Jul 8.

Indiana University Bloomington, United States.

Mechanisms driving adaptive developmental responses to chronic high altitude (HA) exposure are incompletely known. We developed a novel rat model mimicking the human condition of cardiopulmonary adaptation to HA starting at conception and spanning the in utero and post-natal timeframe. We assessed lung growth and cardiopulmonary structure and function, and performed transcriptome analyses to identify mechanisms facilitating developmental adaptations to chronic hypoxia. Read More

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http://dx.doi.org/10.1152/ajplung.00487.2019DOI Listing

DISEQUILIBRIUM BETWEEN THE CLASSIC RENIN-ANGIOTENSIN SYSTEM AND ITS OPPOSING ARM IN SARS-COV-2 RELATED LUNG INJURY.

Am J Physiol Lung Cell Mol Physiol 2020 Jul 8. Epub 2020 Jul 8.

IRCCS INRCA.

A dysregulation of the renin-angiotensin-system (RAS) has been involved in the genesis of lung injury and acute respiratory distress syndrome (ARDS) from different causes, including several viral infections. The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection of pneumocytes, the hallmark of the pandemic coronavirus disease 2019 (COVID-19) involving both alveolar interstitium and capillaries, is linked to angiotensin-converting-enzyme 2 (ACE2) binding and its functional downregulation. ACE2 is a key enzyme for the balance between the two main arms of the RAS: the ACE/Angiotensin (Ang) II/Ang II type 1 receptor axis ("classic RAS"), and the ACE2/Ang 1-7/MasR axis ("anti-RAS"). Read More

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http://dx.doi.org/10.1152/ajplung.00189.2020DOI Listing

Influence of Aminoacyl tRNA Synthetase Complex Interacting Multifunctional Protein 1 on Epithelial Differentiation and Organization During Lung Development.

Am J Physiol Lung Cell Mol Physiol 2020 Jun 24. Epub 2020 Jun 24.

Departments of Cellular and Integrative Physiology and Pediatrics, Indiana University School of Medicine, South Bend, IN, 46617, USA. Department of Chemistry and Biochemistry, University of Notre Dame, South Bend, IN, 46617.

Proper development of the respiratory bronchiole and alveolar epithelium proceeds through coordinated crosstalk between the interface of epithelium and neighboring mesenchyme. Signals that facilitate and coordinate the crosstalk as the bronchial forming canalicular stage transitions to construction of air-exchanging, capillary-alveoli niche in the alveolar stage are poorly understood. Expressed within this decisive region, levels of Aminoacyl tRNA Synthetase Complex Interacting Multifunctional Protein 1 (AIMP1) inversely correlates with the maturation of the lung. Read More

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http://dx.doi.org/10.1152/ajplung.00518.2019DOI Listing

Vascular Permeability Disruption Explored in the Proteomes of Mouse Lungs and Human Microvascular Cells following Acute Bromine Exposure.

Am J Physiol Lung Cell Mol Physiol 2020 Jun 24. Epub 2020 Jun 24.

University of Alabama at Birmingham.

Bromine (Br) is an organohalide found in nature and is integral to many manufacturing processes. Br is toxic to living organisms and high concentrations can prove fatal. To meet industrial demand large amounts of purified Br are produced, transported, and stored worldwide providing a multitude of interfaces for potential human exposure through either accidents or terrorism. Read More

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http://dx.doi.org/10.1152/ajplung.00196.2020DOI Listing

Exoenzyme Y induces extracellular active caspase-7 accumulation independent from apoptosis: Modulation of transmissible cytotoxicity.

Am J Physiol Lung Cell Mol Physiol 2020 Jun 24. Epub 2020 Jun 24.

Physiology and Cell Biology and Internal Medicine, Center for Lung Biology, University of South Alabama, United States.

Caspases-3 and -7 are executioner caspases whose enzymatic activity is necessary to complete apoptotic cell death. Here, we questioned whether endothelial cell infection leads to caspase-3/7-mediated cell death. Pulmonary microvascular endothelial cells (PMVECs) were infected with Pseudomonas aeruginosa (PA103). Read More

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http://dx.doi.org/10.1152/ajplung.00508.2019DOI Listing

Impact of high tidal volume ventilation on surfactant metabolism and lung injury in infant rats.

Am J Physiol Lung Cell Mol Physiol 2020 Jun 24. Epub 2020 Jun 24.

Intensive Care Medicine and Neonatology, University Children's Hospital Zurich, Switzerland.

The poorly understood tolerance towards high tidal volume (V) ventilation observed in critically ill children and age-equivalent animal models may be explained by surfactant homeostasis. The aim of our prospective animal study was to test whether high V with adequate positive end-expiratory pressure (PEEP) is associated with surfactant de novo synthesis and secretion leading to improved lung function and whether extreme mechanical ventilation affects intracellular lamellar body formation and exocytosis. Fourteen days old rats were allocated to five groups: non-ventilated controls, PEEP 5 cmHO with V of 8, 16, and 24 mL/kg, respectively, and PEEP 1 cmHO with V 24 mL/kg. Read More

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http://dx.doi.org/10.1152/ajplung.00043.2020DOI Listing

Antenatal PPARγ Agonist Pioglitazone Stimulates Fetal Lung Maturation Equally in Males and Females.

Am J Physiol Lung Cell Mol Physiol 2020 Jun 24. Epub 2020 Jun 24.

Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, United States.

Antenatal steroids (ANS) accelerate fetal lung maturation and reduce the incidence of respiratory distress syndrome. However, sex-specificity, i.e. Read More

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http://dx.doi.org/10.1152/ajplung.00376.2018DOI Listing

Everyone must be able to breathe: a plan to support diversity and inclusion in respiratory physiology.

Am J Physiol Lung Cell Mol Physiol 2020 Jul 17;319(1):L159-L162. Epub 2020 Jun 17.

Department of Ecology, Evolution, and Organismal Biology, Kennesaw State University, Kennesaw, Georgia.

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http://dx.doi.org/10.1152/ajplung.00269.2020DOI Listing

NOVEL INSIGHTS ON THE PULMONARY VASCULAR CONSEQUENCES OF COVID-19.

Am J Physiol Lung Cell Mol Physiol 2020 Jun 17. Epub 2020 Jun 17.

Pulmonary Hypertension and Vascular Biology Research Group, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Department of Medicine, Québec.

In the last few months, the number of cases of a new coronavirus-related disease (COVID-19) rose exponentially, reaching the status of a pandemic. Interestingly, early imaging studies documented that pulmonary vascular thickening was specifically associated with COVID-19 pneumonia, implying a potential tropism of the virus for the pulmonary vasculature. Moreover, SARS-CoV-2 infection is associated with inflammation, hypoxia, oxidative stress, mitochondrial dysfunction, DNA damage and lung coagulopathy promoting endothelial dysfunction and microthrombosis. Read More

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http://dx.doi.org/10.1152/ajplung.00195.2020DOI Listing
June 2020
4.080 Impact Factor

Selection of Reference Genes for Quantitative PCR: Identifying Reference Genes for Airway Epithelial Cells Exposed to Pseudomonas aeruginosa.

Am J Physiol Lung Cell Mol Physiol 2020 Jun 10. Epub 2020 Jun 10.

Microbiology and Immunology, Geisel School of Medicine at Dartmouth, United States.

Most q-PCR experiments report differential expression relative to the expression of one or more reference genes. Therefore, when experimental conditions alter reference gene expression, q-PCR results may be compromised. Little is known about the magnitude of this problem in practice. Read More

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http://dx.doi.org/10.1152/ajplung.00158.2020DOI Listing

Spermidine supplementation and voluntary activity differentially affect obesity-related structural changes in the mouse lung.

Am J Physiol Lung Cell Mol Physiol 2020 Jun 10. Epub 2020 Jun 10.

Hannover Medical School, Institute of Functional and Applied Anatomy, Germany.

Obesity is associated with lung function impairment and respiratory diseases; however, the underlying pathophysiological mechanisms are still elusive and therapeutic options are limited. This study examined the effects of prolonged excess fat intake on lung mechanics and microstructure and tested spermidine supplementation and physical activity as intervention strategies. C57BL/6N mice fed control diet (CD, 10% fat) or high fat diet (HFD, 60% fat) were left untreated, were supplemented with 3 mM spermidine, had access to running wheels for voluntary activity or a combination of both. Read More

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http://dx.doi.org/10.1152/ajplung.00423.2019DOI Listing

Is targeting Akt a viable option to treat advanced-stage COVID-19 patients?

Am J Physiol Lung Cell Mol Physiol 2020 07 10;319(1):L45-L47. Epub 2020 Jun 10.

Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia, Augusta, Georgia.

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http://dx.doi.org/10.1152/ajplung.00124.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7324934PMC

Heparin as a Therapy for COVID-19: Current Evidence and Future Possibilities.

Am J Physiol Lung Cell Mol Physiol 2020 Jun 10. Epub 2020 Jun 10.

University of Colorado Denver.

Coronavirus Disease 2019 (COVID-19), the clinical syndrome associated with infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has impacted nearly every country in the world. Despite an unprecedented focus of scientific investigation, there is a paucity of evidence-based pharmacotherapies against this disease. Due to this lack of data-driven treatment strategies, broad variations in practice patterns have emerged. Read More

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http://dx.doi.org/10.1152/ajplung.00199.2020DOI Listing

THE EX-VIVO PERFUSED HUMAN LUNG IS RESISTANT TO INJURY BY HIGH-DOSE S. PNEUMONIAE BACTEREMIA.

Am J Physiol Lung Cell Mol Physiol 2020 Jun 10. Epub 2020 Jun 10.

Departments of Medicine and Anesthesiology and the Cardiovascular Research Institute, University of California, San Francisco, California.

Few patients with bacteremia from a non-pulmonary source develop ARDS. However, the mechanisms that protect the lung from injury in bacteremia have not been identified. We simulated bacteremia by adding S. Read More

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http://dx.doi.org/10.1152/ajplung.00053.2020DOI Listing

Consideration of Pannexin 1 channels in COVID-19 pathology and treatment.

Am J Physiol Lung Cell Mol Physiol 2020 07 10;319(1):L121-L125. Epub 2020 Jun 10.

Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, Virginia.

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http://dx.doi.org/10.1152/ajplung.00146.2020DOI Listing

The enigmatic role of TIPE2 in asthma.

Am J Physiol Lung Cell Mol Physiol 2020 Jul 3;319(1):L163-L172. Epub 2020 Jun 3.

Department of Respiratory Medicine, The Second Hospital of Jilin University, Changchun, Jilin, China.

Unlike other members of the tumor necrosis factor (TNF)-α-induced protein 8 (TNFAIP8/TIPE) family that play a carcinogenic role and regulate apoptosis, TNFAIP8-like 2 (TIPE2) can not only maintain immune homeostasis but also regulate inflammation. TIPE2 mainly restrains the activation of T cell receptor (TCR) and Toll-like receptors (TLR), regulating its downstream signaling pathways, thereby regulating inflammation. Interestingly, TIPE2 is abnormally expressed in many inflammatory diseases and may promote or inhibit inflammation in different diseases. Read More

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http://dx.doi.org/10.1152/ajplung.00069.2020DOI Listing
July 2020
4.080 Impact Factor

Thoughts on the alveolar phase of COVID-19.

Authors:
Robert J Mason

Am J Physiol Lung Cell Mol Physiol 2020 07 3;319(1):L115-L120. Epub 2020 Jun 3.

National Jewish Health, Denver, Colorado.

COVID-19 can be divided into three clinical stages, and one can speculate that these stages correlate with where the infection resides. For the asymptomatic phase, the infection mostly resides in the nose, where it elicits a minimal innate immune response. For the mildly symptomatic phase, the infection is mostly in the pseudostratified epithelium of the larger airways and is accompanied by a more vigorous innate immune response. Read More

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http://dx.doi.org/10.1152/ajplung.00126.2020DOI Listing

Protein Tyrosine Phosphatase-α Amplifies TGF-β-Dependent Pro-Fibrotic Signaling in Lung Fibroblasts.

Am J Physiol Lung Cell Mol Physiol 2020 Jun 3. Epub 2020 Jun 3.

Academic Affairs, National Jewish Health, United States.

Idiopathic Pulmonary Fibrosis (IPF) is a progressive fibrosing lung disease for which treatment remains suboptimal. Fibrogenic cytokines, including transforming growth factor-β, are central to its pathogenesis. Protein Tyrosine Phosphatase-alpha (PTPα) has emerged as a key regulator of fibrogenic signaling in fibroblasts. Read More

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http://dx.doi.org/10.1152/ajplung.00235.2019DOI Listing

Measuring the efficiency of pulmonary gas exchange using expired gas instead of arterial blood: Comparing the "ideal" PO2 of Riley with end-tidal PO2.

Am J Physiol Lung Cell Mol Physiol 2020 Jun 3. Epub 2020 Jun 3.

Department of Medicine and Radiology, University of California, San Diego, United States.

When using a new noninvasive method for measuring the efficiency of pulmonary gas exchange, a key measurement is the oxygen deficit, defined as the difference between the end-tidal alveolar PO2 and the calculated arterial PO2. The end-tidal PO2 is measured using a rapid gas analyzer, and the arterial PO2 is derived from pulse oximetry after allowing for the effect of the PCO2 on the oxygen affinity of hemoglobin. In the present report we show that the values of end-tidal PO2 and PCO2 are highly reproducible providing a solid foundation for the measurement of the oxygen deficit. Read More

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http://dx.doi.org/10.1152/ajplung.00150.2020DOI Listing

Understanding the age divide in COVID-19: why are children overwhelmingly spared?

Am J Physiol Lung Cell Mol Physiol 2020 07 3;319(1):L39-L44. Epub 2020 Jun 3.

Department of Pediatric Surgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas.

The rapid emergence and subsequent global dissemination of SARS-CoV-2 disease (COVID-19) has resulted in over 4 million cases worldwide. The disease has a marked predilection for adults, and children are relatively spared. Understanding the age-based differences in pathophysiological pathways and processes relevant to the onset and progression of disease both in the clinical course and in experimental disease models may hold the key to the identification of therapeutic targets. Read More

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http://dx.doi.org/10.1152/ajplung.00183.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7324935PMC

P-selectin blockade in COVID-19-related ARDS.

Am J Physiol Lung Cell Mol Physiol 2020 06;318(6):L1237-L1238

Centro Dipartimentale di Biologia Cellulare Cardiorespiratoria, Dipartimento di Patologia Chirurgica, Medica, Molecolare e dell'Area Critica and Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.

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http://dx.doi.org/10.1152/ajplung.00202.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7276981PMC

Link between increased cellular senescence and extracellular matrix changes in COPD.

Am J Physiol Lung Cell Mol Physiol 2020 Jul 27;319(1):L48-L60. Epub 2020 May 27.

Department of Pathology and Medical Biology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.

Chronic obstructive pulmonary disease (COPD) is associated with features of accelerated aging, including cellular senescence, DNA damage, oxidative stress, and extracellular matrix (ECM) changes. We propose that these features are particularly apparent in patients with severe, early-onset (SEO)-COPD. Whether fibroblasts from COPD patients display features of accelerated aging and whether this is also present in relatively young SEO-COPD patients is unknown. Read More

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http://dx.doi.org/10.1152/ajplung.00028.2020DOI Listing

MitoTEMPOL, a Mitochondrial Targeted Antioxidant, Prevents Sepsis Induced Diaphragm Dysfunction.

Am J Physiol Lung Cell Mol Physiol 2020 May 27. Epub 2020 May 27.

Department of Internal Medicine, University of Kentucky, United States.

Clinical studies indicate that sepsis induced diaphragm dysfunction is a major contributor to respiratory failure in mechanically ventilated patients. Currently there is no drug to treat this form of diaphragm weakness. Sepsis induced muscle dysfunction is thought to be triggered by excessive mitochondrial free radical generation, we therefore hypothesized that therapies which target mitochondrial free radical production may prevent sepsis induced diaphragm weakness. Read More

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http://dx.doi.org/10.1152/ajplung.00473.2019DOI Listing

Glucocorticoid Regulates Mesenchymal Cell Differentiation Required for Perinatal Lung Morphogenesis and Function.

Am J Physiol Lung Cell Mol Physiol 2020 May 27. Epub 2020 May 27.

The Perinatal Institute and Section of Neonatology, Perinatal and Pulmonary Biology, Cincinnati Children's Hospital Medical Center, United States.

While antenatal glucocorticoids are widely used to enhance lung function in preterm infants, cellular and molecular mechanisms by which glucocorticoid receptor (GR) signaling influences lung maturation remain poorly understood. Deletion of the glucocorticoid receptor gene (Nr3c1) from fetal pulmonary mesenchymal cells phenocopied defects caused by global Nr3c1 deletion, while lung epithelial- or endothelial-specific Nr3c1 deletion did not impair lung function at birth. We integrated genome-wide gene expression profiling, ATAC-seq, and single cell RNA-seq data in mice in which GR was deleted or activated to identify the cellular and molecular mechanisms by which glucocorticoids control prenatal lung maturation. Read More

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http://dx.doi.org/10.1152/ajplung.00459.2019DOI Listing
May 2020
4.080 Impact Factor

The FOXA1 transcriptional network coordinates key functions of primary human airway epithelial cells.

Am J Physiol Lung Cell Mol Physiol 2020 Jul 20;319(1):L126-L136. Epub 2020 May 20.

Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, Ohio.

The differentiated functions of the human airway epithelium are coordinated by a complex network of transcription factors. These include the pioneer factors Forkhead box A1 and A2 (FOXA1 and FOXA2), which are well studied in several tissues, but their role in airway epithelial cells is poorly characterized. Here, we define the cistrome of FOXA1 and FOXA2 in primary human bronchial epithelial (HBE) cells by chromatin immunoprecipitation with deep-sequencing (ChIP-seq). Read More

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http://dx.doi.org/10.1152/ajplung.00023.2020DOI Listing

Structure and activity of human surfactant protein D from different natural sources.

Am J Physiol Lung Cell Mol Physiol 2020 Jul 20;319(1):L148-L158. Epub 2020 May 20.

Department of Biochemistry, Faculty of Biology, Complutense University, Madrid, Spain.

Surfactant protein D (SP-D) is a C-type lectin that participates in the innate immune defense of lungs. It binds pathogens through its carbohydrate recognition domain in a calcium-dependent manner. Human surfactant protein D (hSP-D) has been routinely obtained from bronchoalveolar lavage of patients suffering from pulmonary alveolar proteinosis (PAP) and from amniotic fluid (AF). Read More

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http://dx.doi.org/10.1152/ajplung.00007.2020DOI Listing

S100A4 is secreted by airway smooth muscle tissues and activates inflammatory signaling pathways via receptors for advanced glycation end products.

Am J Physiol Lung Cell Mol Physiol 2020 Jul 20;319(1):L185-L195. Epub 2020 May 20.

Department of Anatomy, Cell Biology and Physiology, Indiana University School of Medicine, Indianapolis, Indiana.

S100A4 is a low-molecular-mass (12 kDa) EF-hand Ca-binding S100 protein that is expressed in a broad range of normal tissue and cell types. S100A4 can be secreted from some cells to act in an autocrine or paracrine fashion on target cells and tissues. S100A4 has been reported in the extracellular fluids of subjects with several inflammatory diseases, including asthma. Read More

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http://dx.doi.org/10.1152/ajplung.00347.2019DOI Listing

Genome-wide integration of microRNA and transcriptomic profiles of differentiating human alveolar epithelial cells.

Am J Physiol Lung Cell Mol Physiol 2020 Jul 20;319(1):L173-L184. Epub 2020 May 20.

Hastings Center for Pulmonary Research and Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.

The alveolar epithelium is comprised of two cell types, alveolar epithelial type 1 (AT1) and type 2 (AT2) cells, the latter being capable of self-renewal and transdifferentiation into AT1 cells for normal maintenance and restoration of epithelial integrity following injury. MicroRNAs (miRNAs) are critical regulators of several biological processes, including cell differentiation; however, their role in establishment/maintenance of cellular identity in adult alveolar epithelium is not well understood. To investigate this question, we performed genome-wide analysis of sequential changes in miRNA and gene expression profiles using a well-established model in which human AT2 (hAT2) cells transdifferentiate into AT1-like cells over time in culture that recapitulates many aspects of transdifferentiation in vivo. Read More

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http://dx.doi.org/10.1152/ajplung.00519.2019DOI Listing

Estrogen regulates the expression of SARS-CoV-2 receptor ACE2 in differentiated airway epithelial cells.

Am J Physiol Lung Cell Mol Physiol 2020 06 20;318(6):L1280-L1281. Epub 2020 May 20.

Division of Allergic Diseases, Mayo Clinic, Rochester, Minnesota.

There is marked sexual dimorphism in the current coronavirus disease 2019 (COVID-19) pandemic. Here we report that estrogen can regulate the expression of angiotensin-converting enzyme 2 (ACE2), a key component for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cell entry, in differentiated airway epithelial cells. Further studies are required to elucidate the mechanisms by which sex steroids regulate SARS-CoV-2 infectivity. Read More

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http://dx.doi.org/10.1152/ajplung.00153.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7276982PMC

MUC1 contributes to goblet cell metaplasia and MUC5AC expression in response to cigarette smoke in vivo.

Am J Physiol Lung Cell Mol Physiol 2020 Jul 13;319(1):L82-L90. Epub 2020 May 13.

Department of Otolaryngology, University of Arizona College of Medicine, Tucson, Arizona.

Goblet cell metaplasia (GCM) and mucin overproduction are a hallmark of chronic rhinosinusitis (CRS) and chronic obstructive pulmonary disease (COPD). In the airways, cigarette smoke (CS) induces activation of the epidermal growth factor receptor (EGFR) leading to GCM and overexpression of the gel-forming mucin MUC5AC. Although previous studies have demonstrated that a membrane-bound mucin, MUC1, modulates the activation of CS-induced EGFR, the role of MUC1 in CS-induced GCM and mucin overproduction has not been explored. Read More

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http://dx.doi.org/10.1152/ajplung.00049.2019DOI Listing

Oxygen deficit is a sensitive measure of mild gas exchange impairment at inspired O between 12.5% and 21.

Am J Physiol Lung Cell Mol Physiol 2020 Jul 13;319(1):L91-L94. Epub 2020 May 13.

Department of Medicine, University of California, San Diego, La Jolla, California.

The oxygen deficit (OD) is the difference between the end-tidal alveolar Po and the calculated Po of arterial blood based on measured oxygen saturation that acts as a proxy for the alveolar-arterial Po difference. Previous work has shown that the alveolar gas meter (AGM100) can measure pulmonary gas exchange, via the OD, in patients with a history of lung disease and in normal subjects breathing 12.5% O. Read More

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http://dx.doi.org/10.1152/ajplung.00003.2020DOI Listing

Caspase-11 contributes to pulmonary host defense against and local activation of coagulation.

Am J Physiol Lung Cell Mol Physiol 2020 Jul 13;319(1):L105-L114. Epub 2020 May 13.

Center of Experimental and Molecular Medicine, Amsterdam, The Netherlands.

is a common cause of gram-negative pneumonia and sepsis. Caspase-11 is an intracellular receptor for lipopolysaccharide and regulates pyroptosis, a specific form of inflammatory cell death, which aids in host defense against intracellular gram-negative bacteria. Recently, caspase-11 has also been implicated in blood coagulation. Read More

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http://dx.doi.org/10.1152/ajplung.00422.2019DOI Listing

Urgent reconsideration of lung edema as a preventable outcome in COVID-19: inhibition of TRPV4 represents a promising and feasible approach.

Am J Physiol Lung Cell Mol Physiol 2020 06 13;318(6):L1239-L1243. Epub 2020 May 13.

Department of Anesthesiology, Duke University, Durham, North Carolina.

Lethality of coronavirus disease (COVID-19) during the 2020 pandemic, currently still in the exponentially accelerating phase in most countries, is critically driven by disruption of the alveolo-capillary barrier of the lung, leading to lung edema as a direct consequence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We argue for inhibition of the transient receptor potential vanilloid 4 (TRPV4) calcium-permeable ion channel as a strategy to address this issue, based on the rationale that TRPV4 inhibition is protective in various preclinical models of lung edema and that TRPV4 hyperactivation potently damages the alveolo-capillary barrier, with lethal outcome. We believe that TRPV4 inhibition has a powerful prospect at protecting this vital barrier in COVID-19 patients, even to rescue a damaged barrier. Read More

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http://dx.doi.org/10.1152/ajplung.00161.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7276984PMC

Lung-Resident Mesenchymal Stromal Cells are Tissue-Specific Regulators of Lung Homeostasis.

Am J Physiol Lung Cell Mol Physiol 2020 May 13. Epub 2020 May 13.

Division of Biomedical Sciences, University of California Riverside, United States.

Until recently, data supporting the tissue-resident status of mesenchymal stromal cells (MSC) has been ambiguous since their discovery in the 1950-60s. These progenitor cells were first discovered as bone marrow-derived adult multipotent cells and believed to migrate to sites of injury, opposing the notion that they are residents of all tissue types. In recent years, however, it has been demonstrated that MSC can be found in all tissues and MSC from different tissues represent distinct populations with differential protein expression unique to each tissue type. Read More

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http://dx.doi.org/10.1152/ajplung.00049.2020DOI Listing

Surfactant-secreted phospholipase A interplay and respiratory outcome in preterm neonates.

Am J Physiol Lung Cell Mol Physiol 2020 Jul 13;319(1):L95-L104. Epub 2020 May 13.

Cystic fibrosis and Bronchial diseases team-INSERM U938, Institut Pasteur, Paris, France.

Secreted phospholipase A hydrolyzes surfactant phospholipids and is crucial for the inflammatory cascade; preterm neonates are treated with exogenous surfactant, but the interaction between surfactant and phospholipase is unknown. We hypothesize that this interplay is complex and the enzyme plays a relevant role in neonates needing surfactant replacement. We aimed to: ) identify phospholipases A isoforms expressed in preterm lung; ) study the enzyme role on surfactant retreatment and function and the effect of exogenous surfactant on the enzyme system; and ) verify whether phospholipase A is linked to respiratory outcomes. Read More

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http://dx.doi.org/10.1152/ajplung.00462.2019DOI Listing

Treatment of COVID-19-exacerbated asthma: should systemic corticosteroids be used?

Am J Physiol Lung Cell Mol Physiol 2020 06 13;318(6):L1244-L1247. Epub 2020 May 13.

National Heart and Lung Institute, Imperial College London, London, United Kingdom.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a new rapidly spreading infectious disease. Current guidance from the World Health Organization (WHO) highlights asthmatics as a high-risk group for severe illness from COVID-19. Viruses are common triggers of asthma exacerbations and the current SARS-CoV-2 pandemic raises several questions regarding the optimum management strategies. Read More

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http://dx.doi.org/10.1152/ajplung.00144.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7276980PMC

Upregulation of airway smooth muscle calcium-sensing receptor by low-molecular-weight hyaluronan: translational research impact.

Authors:
Saumya Pandey

Am J Physiol Lung Cell Mol Physiol 2020 05;318(5):L1109-L1110

Department of Clinical Research, Indira-IVF Hospital, Udaipur, India.

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http://dx.doi.org/10.1152/ajplung.00078.2020DOI Listing

IL-1β dysregulates cGMP signaling in the newborn lung.

Am J Physiol Lung Cell Mol Physiol 2020 May 6. Epub 2020 May 6.

CVRC - MGH East, Massachusetts General Hospital, United States.

Cyclic guanosine monophosphate (cGMP) signaling is an important regulator of newborn lung function and development. Although cGMP signaling is decreased in many models of newborn lung injury, the mechanisms are poorly understood. We determined how IL-1β regulates the expression of the α1-subunit of soluble guanylate cyclase (sGCα1), a prime effector of pulmonary cGMP signaling. Read More

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http://dx.doi.org/10.1152/ajplung.00382.2019DOI Listing

Airway Remodeling in Ferrets with Cigarette Smoke Induced COPD using µCT Imaging.

Am J Physiol Lung Cell Mol Physiol 2020 May 6. Epub 2020 May 6.

Deparment of Medicine and the Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama, Birmingham, United States.

Rationale: Structural changes to airway morphology such as increased bronchial wall thickness (BWT) and airway wall area are cardinal features of chronic obstructive pulmonary disease (COPD). Ferrets are a recently established animal model uniquely exhibiting similar clinical and pathological characteristics of COPD as humans, including chronic bronchitis.

Objectives: Develop a µCT method for evaluating structural changes to the airways in ferrets, and assess whether the effects of smoking induce changes consistent with chronic bronchitis in humans. Read More

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http://dx.doi.org/10.1152/ajplung.00328.2019DOI Listing

Overexpression of in mice leads to altered lung alveolar development and worsens lesions induced by hyperoxia.

Am J Physiol Lung Cell Mol Physiol 2020 Jul 6;319(1):L71-L81. Epub 2020 May 6.

Service de Pneumologie et d'Allergologie Pédiatriques, Hôpital Universitaire Necker-Enfants Malades, Assistance Publique - Hôpitaux de Paris, Paris, France.

SPARC/osteonectin, cwcv and kazal-like domains proteoglycan 2 () was previously associated with genetic susceptibility to bronchopulmonary dysplasia in a French population of very preterm neonates. Its expression increases during lung development and is increased after exposure of rat pups to hyperoxia compared with controls bred in room air. To further investigate the role of SPOCK2 during lung development, we designed two mouse models, one that uses a specific anti-Spock2 antibody and one that reproduces the hyperoxia-induced expression with a transgenic mouse model resulting in a conditional and lung-targeted overexpression of . Read More

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http://dx.doi.org/10.1152/ajplung.00191.2019DOI Listing

Reply to Letter to the Editor: "COVID-19: is the ACE2 just a foe?"

Am J Physiol Lung Cell Mol Physiol 2020 05;318(5):L1031

Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel.

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http://dx.doi.org/10.1152/ajplung.00134.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7203571PMC

Rigor before speculation in COVID-19 therapy.

Am J Physiol Lung Cell Mol Physiol 2020 05;318(5):L1027-L1028

Department of Medicine, Duke University School of Medicine, and Durham Veterans Affairs Medical Centers, Durham, North Carolina.

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http://dx.doi.org/10.1152/ajplung.00152.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7203572PMC

Don't judge too RAShly: the multifaceted role of the renin-angiotensin system and its therapeutic potential in COVID-19.

Am J Physiol Lung Cell Mol Physiol 2020 05;318(5):L1023-L1024

Institute of Physiology, Charité-Universitätsmedizin Berlin, Berlin, Germany.

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http://dx.doi.org/10.1152/ajplung.00118.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7215092PMC

Normal murine respiratory tract has its mucus concentrated in clouds based on the Muc5b mucin.

Am J Physiol Lung Cell Mol Physiol 2020 Jun 29;318(6):L1270-L1279. Epub 2020 Apr 29.

Department of Medical Biochemistry, University of Gothenburg, Gothenburg, Sweden.

The organization of the normal airway mucus system differs in small experimental animals from that in humans and large mammals. To address normal murine airway mucociliary clearance, Alcian blue-stained mucus transport was measured ex vivo on tracheal tissues of naïve C57BL/6, , , and EGFP-tagged Muc5b reporter mice. Close to the larynx with a few submucosal glands, the mucus appeared as thick bundles. Read More

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http://dx.doi.org/10.1152/ajplung.00485.2019DOI Listing

Circulating miRNA 887 is differentially expressed in ARDS and modulates endothelial function.

Am J Physiol Lung Cell Mol Physiol 2020 Jun 22;318(6):L1261-L1269. Epub 2020 Apr 22.

Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, South Carolina.

Circulating microRNAs (miRNAs) can be taken up by recipient cells and have been recently associated with the acute respiratory distress syndrome (ARDS). Their role in host predisposition to the syndrome is unknown. The objective of the study was to identify circulating miRNAs associated with the development of sepsis-related ARDS and examine their impact on endothelial cell gene expression and function. Read More

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http://dx.doi.org/10.1152/ajplung.00494.2019DOI Listing

Alveolar heparan sulfate shedding impedes recovery from bleomycin-induced lung injury.

Am J Physiol Lung Cell Mol Physiol 2020 Jun 22;318(6):L1198-L1210. Epub 2020 Apr 22.

Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado.

The pulmonary epithelial glycocalyx, an anionic cell surface layer enriched in glycosaminoglycans such as heparan sulfate and chondroitin sulfate, contributes to the alveolar barrier. Direct injury to the pulmonary epithelium induces shedding of heparan sulfate into the air space; the impact of this shedding on recovery after lung injury is unknown. Using mass spectrometry, we found that heparan sulfate was shed into the air space for up to 3 wk after intratracheal bleomycin-induced lung injury and coincided with induction of matrix metalloproteinases (MMPs), including MMP2. Read More

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http://dx.doi.org/10.1152/ajplung.00063.2020DOI Listing

The importance of reporting house dust mite endotoxin abundance: impact on the lung transcriptome.

Am J Physiol Lung Cell Mol Physiol 2020 Jun 22;318(6):L1229-L1236. Epub 2020 Apr 22.

Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, Manitoba, Canada.

The abundance of lipopolysaccharide (LPS) in house dust mite (HDM) preparations is broad and mirrors the variability seen in the homes of people with asthma. LPS in commercially available stocks ranges from 31 to 5,2000 endotoxin units. The influence of vastly different LPS loads on the mechanisms that define the immune and inflammatory phenotype of HDM-challenged mice has not been defined. Read More

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http://dx.doi.org/10.1152/ajplung.00103.2020DOI Listing