{delta}{beta}{gamma}-ENaC is inhibited by CFTR but stimulated by cAMP in Xenopus laevis oocytes
In conclusion, our results demonstrate that β-ENaC is inhibited by CFTR but activated by cAMP. (Source: AJP: Lung Cellular and Molecular Physiology)
Source: AJP: Lung Cellular and Molecular Physiology - February 7, 2017 Category: Respiratory Medicine Authors: Rauh, R., Hoerner, C., Korbmacher, C. Tags: RESEARCH ARTICLE Source Type: research

BMI-1 extends proliferative potential of human bronchial epithelial cells while retaining their mucociliary differentiation capacity
Air-liquid interface (ALI) culture of primary airway epithelial cells enables mucociliary differentiation providing an in vitro model of the human airway, but their proliferative potential is limited. To extend proliferation, these cells were previously transduced with viral oncogenes or mouse Bmi-1 + hTERT, but the resultant cell lines did not undergo mucociliary differentiation. We hypothesized that use of human BMI-1 alone would increase the proliferative potential of bronchial epithelial cells while retaining their mucociliary differentiation potential. Cystic fibrosis (CF) and non-CF bronchial epithelial cells were tr...
Source: AJP: Lung Cellular and Molecular Physiology - February 7, 2017 Category: Respiratory Medicine Authors: Munye, M. M., Shoemark, A., Hirst, R. A., Delhove, J. M., Sharp, T. V., McKay, T. R., OCallaghan, C., Baines, D. L., Howe, S. J., Hart, S. L. Tags: RESEARCH ARTICLE Source Type: research

Digital 3D reconstructions using histological serial sections of lung tissue including the alveolar capillary network
Grothausmann R, Knudsen L, Ochs M, Mühlfeld C. Digital 3D reconstructions using histological serial sections of lung tissue including the alveolar capillary network. Am J Physiol Lung Cell Mol Physiol 312: L243–L257, 2017. First published December 2, 2016; doi:10.1152/ajplung.00326.2016.—The alveolar capillary network (ACN) provides an enormously large surface area that is necessary for pulmonary gas exchange. Changes of the ACN during normal or pathological development or in pulmonary diseases are of great functional impact and warrant further analysis. Due to the complexity of the three-dimensional (3...
Source: AJP: Lung Cellular and Molecular Physiology - February 7, 2017 Category: Respiratory Medicine Authors: Grothausmann, R., Knudsen, L., Ochs, M., Mühlfeld, C. Tags: RESEARCH ARTICLE Source Type: research

Depletion of circulating monocytes suppresses IL-17 and HMGB1 expression in mice with LPS-induced acute lung injury
Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is an important cause of mortality in critically ill patients. Macrophages play an important role in the pathogenesis of ALI/ARDS. To investigate the role and underlying mechanisms of circulating monocytes and resident alveolar macrophages (AMs) in ALI/ARDS, we depleted circulating monocytes and AMs by clodronate-loaded liposome (CL) in a lipopolysaccharide (LPS)-induced ALI/ARDS mouse model. Our results indicated that depletion of circulating monocytes by intravenous injection of CL 2 days before intratracheal LPS treatment significantly suppressed the acute...
Source: AJP: Lung Cellular and Molecular Physiology - February 7, 2017 Category: Respiratory Medicine Authors: Jiang, Z., Zhou, Q., Gu, C., Li, D., Zhu, L. Tags: RESEARCH ARTICLE Source Type: research

Prophylactic and therapeutic treatment with the flavonone sakuranetin ameliorates LPS-induced acute lung injury
This study investigated the preventive and therapeutic effects of sakuranetin on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. Animals were treated with intranasal sakuranetin 30 min before or 6 h after instillation of LPS. Twenty-four hours after ALI was induced, lung function, inflammation, macrophages population markers, collagen fiber deposition, the extent of oxidative stress, and the expression of matrix metalloprotease-9 (MMP-9), tissue inhibitor of MMP-9 (TIMP-1) and NF-B were evaluated. The animals began to show lung alterations 6 h after LPS instillation, and these changes persisted until 24 h...
Source: AJP: Lung Cellular and Molecular Physiology - February 7, 2017 Category: Respiratory Medicine Authors: Bittencourt-Mernak, M. I., Pinheiro, N. M., Santana, F. P. R., Guerreiro, M. P., Saraiva-Romanholo, B. M., Grecco, S. S., Caperuto, L. C., Felizardo, R. J. F., Camara, N. O. S., Tiberio, I. F. L. C., Martins, M. A., Lago, J. H. G., Prado, C. M. Tags: RESEARCH ARTICLE Source Type: research

Intermittent hypoxia during recovery from neonatal hyperoxic lung injury causes long-term impairment of alveolar development: A new rat model of BPD
Bronchopulmonary dysplasia (BPD) is a chronic lung injury characterized by impaired alveologenesis that may persist into adulthood. Rat models of BPD using varying degrees of hyperoxia to produce injury either cause early mortality or spontaneously recover following removal of the inciting stimulus, thus limiting clinical relevance. We sought to refine an established rat model induced by exposure to 60% O2 from birth by following hyperoxia with intermittent hypoxia (IH). Rats exposed from birth to air or 60% O2 until day 14 were recovered in air with or without IH (FIO2 = 0.10 for 10 min every 6 h) until day 28. Animals ex...
Source: AJP: Lung Cellular and Molecular Physiology - January 31, 2017 Category: Respiratory Medicine Authors: Mankouski, A., Kantores, C., Wong, M. J., Ivanovska, J., Jain, A., Benner, E. J., Mason, S. N., Tanswell, A. K., Auten, R. L., Jankov, R. P. Tags: RAPID REPORT Source Type: research

Cartilage rings contribute to the proper embryonic tracheal epithelial differentiation, metabolism, and expression of inflammatory genes
The signaling cross talk between the tracheal mesenchyme and epithelium has not been researched extensively, leaving a substantial gap of knowledge in the mechanisms dictating embryonic development of the proximal airways by the adjacent mesenchyme. Recently, we reported that embryos lacking mesenchymal expression of Sox9 did not develop tracheal cartilage rings and showed aberrant differentiation of the tracheal epithelium. Here, we propose that tracheal cartilage provides local inductive signals responsible for the proper differentiation, metabolism, and inflammatory status regulation of the tracheal epithelium. The trac...
Source: AJP: Lung Cellular and Molecular Physiology - January 31, 2017 Category: Respiratory Medicine Authors: Turcatel, G., Millette, K., Thornton, M., Leguizamon, S., Grubbs, B., Shi, W., Warburton, D. Tags: RESEARCH ARTICLE Source Type: research

Posttranslational modification of {beta}-catenin is associated with pathogenic fibroblastic changes in bronchopulmonary dysplasia
We examined fetal lung tissue, lung tissue from term newborns, and lung tissue from infants who died with BPD; we found nuclear β-catenin phosphorylation at Y489 in epithelial and mesenchymal cells in fetal tissue and BPD tissue, but not in the lungs of term infants. Using a 3D human organoid model, we found increased nuclear localization of β-catenin phosphorylated at Y489 (p-β-cateninY489) after exposure to alternating hypoxia and hyperoxia compared with organoids cultured in normoxia. Exogenous stimulation of the canonical Wnt pathway in organoids was sufficient to cause nuclear localization of p-β-c...
Source: AJP: Lung Cellular and Molecular Physiology - January 31, 2017 Category: Respiratory Medicine Authors: Sucre, J. M. S., Vijayaraj, P., Aros, C. J., Wilkinson, D., Paul, M., Dunn, B., Guttentag, S. H., Gomperts, B. N. Tags: RAPID REPORT Source Type: research

Bronchodilatory effect of deep inspiration in freshly isolated sheep lungs
Taking a big breath is known to reverse bronchoconstriction induced by bronchochallenge in healthy subjects; this bronchodilatory effect of deep inspiration (DI) is diminished in asthmatics. The mechanism underlying the DI effect is not clear. Observations from experiments using isolated airway smooth muscle (ASM) preparations and airway segments suggest that straining of ASM due to DI could lead to bronchodilation, possibly due to strain-induced reduction in ASM contractility. However, factors external to the lung cannot be excluded as potential causes for the DI effect. Neural reflex initiated by stretch receptors in the...
Source: AJP: Lung Cellular and Molecular Physiology - January 31, 2017 Category: Respiratory Medicine Authors: Wong, W. D., Wang, L., Pare, P. D., Seow, C. Y. Tags: RESEARCH ARTICLE Source Type: research

Alternative hematological and vascular adaptive responses to high-altitude hypoxia in East African highlanders
In conclusion, the Amhara balance minimally elevated hemoglobin with vasodilatory response to environmental hypoxia, whereas Oromo rely mainly on elevated hemoglobin response. These results point to different combinations of adaptive responses in genetically similar East African highlanders. (Source: AJP: Lung Cellular and Molecular Physiology)
Source: AJP: Lung Cellular and Molecular Physiology - January 31, 2017 Category: Respiratory Medicine Authors: Cheong, H. I., Janocha, A. J., Monocello, L. T., Garchar, A. C., Gebremedhin, A., Erzurum, S. C., Beall, C. M. Tags: RESEARCH ARTICLE Source Type: research

Factor XI deficiency enhances the pulmonary allergic response to house dust mite in mice independent of factor XII
In conclusion, FXI attenuates part of the allergic response to repeated administration of HDM in the airways by a mechanism that is independent of activation via FXII. (Source: AJP: Lung Cellular and Molecular Physiology)
Source: AJP: Lung Cellular and Molecular Physiology - January 31, 2017 Category: Respiratory Medicine Authors: Stroo, I., Yang, J., de Boer, J. D., Roelofs, J. J. T. H., van t Veer, C., Castellino, F. J., Zeerleder, S., van der Poll, T. Tags: RESEARCH ARTICLE Source Type: research

The role of nuclear factor-erythroid 2 related factor 2 (Nrf-2) in the protection against lung injury
Nuclear factor-erythroid 2 related factor 2 (Nrf2) is a ubiquitous master transcription factor that upregulates antioxidant response elements (AREs)-mediated expression of antioxidant enzyme and cytoprotective proteins. Activation of Nrf2 has been shown to be protective against lung injury. In the lung, diverse stimuli including environmental oxidants, medicinal agents, and pathogens can activate Nrf2. Nrf2 translocates to the nucleus and binds to an ARE. Through transcriptional induction of ARE-bearing genes encoding antioxidant-detoxifying proteins, Nrf2 induces cellular rescue pathways against oxidative pulmonary injury...
Source: AJP: Lung Cellular and Molecular Physiology - January 31, 2017 Category: Respiratory Medicine Authors: Zhao, H., Eguchi, S., Alam, A., Ma, D. Tags: REVIEW Source Type: research

CD36 mediates H2O2-induced calcium influx in lung microvascular endothelial cells
In conclusion, our data suggest that CD36 plays an important role in H2O2-mediated lung injury and that the mechanism may involve CD36-dependent scaffolding of Fyn to the cell membrane to facilitate TRPV4 phosphorylation. (Source: AJP: Lung Cellular and Molecular Physiology)
Source: AJP: Lung Cellular and Molecular Physiology - January 9, 2017 Category: Respiratory Medicine Authors: Suresh, K., Servinsky, L., Reyes, J., Undem, C., Zaldumbide, J., Rentsendorj, O., Modekurty, S., Dodd-o, J. M., Scott, A., Pearse, D. B., Shimoda, L. A. Tags: RESEARCH ARTICLE Source Type: research

Region-specific role for Pten in maintenance of epithelial phenotype and integrity
Previous studies have demonstrated resistance to naphthalene-induced injury in proximal airways of mice with lung epithelial-specific deletion of the tumor-suppressor gene Pten, attributed to increased proliferation of airway progenitors. We tested effects of Pten loss following bleomycin injury, a model typically used to study distal lung epithelial injury, in conditional PtenSFTPC-cre knockout mice. Pten-deficient airway epithelium exhibited marked hyperplasia, particularly in small bronchioles and at bronchoalveolar duct junctions, with reduced E-cadherin and β-catenin expression between cells toward the luminal as...
Source: AJP: Lung Cellular and Molecular Physiology - January 9, 2017 Category: Respiratory Medicine Authors: Flodby, P., Liebler, J. M., Sunohara, M., Castillo, D. R., McConnell, A. M., Krishnaveni, M. S., Banfalvi, A., Li, M., Stripp, B., Zhou, B., Crandall, E. D., Minoo, P., Borok, Z. Tags: RESEARCH ARTICLE Source Type: research

Role of IL-17A in murine models of COPD airway disease
Small airway fibrosis is a major pathological feature of chronic obstructive pulmonary disease (COPD) and is refractory to current treatments. Chronic inflammatory cells accumulate around small airways in COPD and are thought to play a major role in small airway fibrosis. Mice deficient in α/β T cells have recently been shown to be protected from both experimental airway inflammation and fibrosis. In these models, CD4+Th17 cells and secretion of IL-17A are increased. However, a pathogenic role for IL-17 in specifically mediating fibrosis around airways has not been demonstrated. Here a role for IL-17A in airway ...
Source: AJP: Lung Cellular and Molecular Physiology - January 9, 2017 Category: Respiratory Medicine Authors: Yanagisawa, H., Hashimoto, M., Minagawa, S., Takasaka, N., Ma, R., Moermans, C., Ito, S., Araya, J., Budelsky, A., Goodsell, A., Baron, J. L., Nishimura, S. L. Tags: RESEARCH ARTICLE Source Type: research