Enrichment of selective miRNAs in exosomes and delivery of exosomal miRNAs in vitro and in vivo
Exosomes are nanovesicles secreted by cells and contain various molecules including protein, lipid, and DNA/RNA. They are crucial mediators of the intercellular communication and serve as promising vehicles for drug delivery and gene therapy. Recently, accumulating evidence suggests that microRNAs (miRNAs) may serve as new and potentially powerful targets for therapeutic interventions against various human diseases. However, steadily and effectively delivering miRNA mimics or inhibitors to target cells remains a major obstacle. To enhance the efficacy of exosome-mediated delivery of miRNA molecules, it is crucial to develo...
Source: AJP: Lung Cellular and Molecular Physiology - January 9, 2017 Category: Respiratory Medicine Authors: Zhang, D., Lee, H., Zhu, Z., Minhas, J. K., Jin, Y. Tags: INNOVATIVE METHODOLOGY Source Type: research

Active vs. sedentary lifestyle from weaning to adulthood and susceptibility to ozone in rats
The prevalence of a sedentary (SED) life style combined with calorically rich diets has spurred the rise in childhood obesity, which, in turn, translates to adverse health effects in adulthood. Obesity and lack of active (ACT) lifestyle may increase susceptibility to air pollutants. We housed 22-day-old female Long-Evans rats in a cage without (SED) or with a running wheel (ACT). After 10 wk the rats ran 310 ± 16.3 km. Responses of SED and ACT rats to whole-body O3 (0, 0.25, 0.5, or 1.0 ppm; 5 h/day for 2 days) was assessed. Glucose tolerance testing (GTT) was performed following the first day of O3. ACT rats had le...
Source: AJP: Lung Cellular and Molecular Physiology - December 31, 2016 Category: Respiratory Medicine Authors: Gordon, C. J., Phillips, P. M., Ledbetter, A., Snow, S. J., Schladweiler, M. C., Johnstone, A. F. M., Kodavanti, U. P. Tags: RESEARCH ARTICLE Source Type: research

TRAIL signaling is proinflammatory and proviral in a murine model of rhinovirus 1B infection
In conclusion, TRAIL promotes RV-induced AHR, inflammation and RV1B replication, implicating this molecule and its downstream signaling pathways as a possible target for the amelioration of RV1B-induced allergic and nonallergic lung inflammation and AHR. (Source: AJP: Lung Cellular and Molecular Physiology)
Source: AJP: Lung Cellular and Molecular Physiology - December 31, 2016 Category: Respiratory Medicine Authors: Girkin, J. L., Hatchwell, L. M., Collison, A. M., Starkey, M. R., Hansbro, P. M., Yagita, H., Foster, P. S., Mattes, J. Tags: RESEARCH ARTICLE Source Type: research

Deformation-induced transitional myofibroblasts contribute to compensatory lung growth
In many mammals, including humans, removal of one lung (pneumonectomy) results in the compensatory growth of the remaining lung. Compensatory growth involves not only an increase in lung size, but also an increase in the number of alveoli in the peripheral lung; however, the process of compensatory neoalveolarization remains poorly understood. Here, we show that the expression of α-smooth muscle actin (SMA)—a cytoplasmic protein characteristic of myofibroblasts—is induced in the pleura following pneumonectomy. SMA induction appears to be dependent on pleural deformation (stretch) as induction is prevented...
Source: AJP: Lung Cellular and Molecular Physiology - December 31, 2016 Category: Respiratory Medicine Authors: Bennett, R. D., Ysasi, A. B., Wagner, W. L., Valenzuela, C. D., Tsuda, A., Pyne, S., Li, S., Grimsby, J., Pokharel, P., Livak, K. J., Ackermann, M., Blainey, P., Mentzer, S. J. Tags: RESEARCH ARTICLE Source Type: research

SIRT3 blocks myofibroblast differentiation and pulmonary fibrosis by preventing mitochondrial DNA damage
This study was undertaken to determine the role of mitochondrial deacetylase SIRT3 in TGF-β1-induced myofibroblast differentiation in vitro and lung fibrosis in vivo. Treatment of human lung fibroblasts with TGF-β1 resulted in increased expression of fibrosis markers, smooth muscle α-actin (α-SMA), collagen-1, and fibronectin. TGF-β1 treatment also caused depletion of endogenous SIRT3, which paralleled with increased production of reactive oxygen species (ROS), DNA damage, and subsequent reduction in levels of 8-oxoguanine DNA glycosylase (OGG1), an enzyme that hydrolyzes oxidized guanine (8-oxo-...
Source: AJP: Lung Cellular and Molecular Physiology - December 31, 2016 Category: Respiratory Medicine Authors: Bindu, S., Pillai, V. B., Kanwal, A., Samant, S., Mutlu, G. M., Verdin, E., Dulin, N., Gupta, M. P. Tags: RESEARCH ARTICLE Source Type: research

Double-hit mouse model of cigarette smoke priming for acute lung injury
In this study, using two strains of mice, we characterized a double-hit mouse model of ALI induced by CS priming of injury caused by lipopolysaccharide (LPS). C57BL/6 and AKR mice were preexposed to CS briefly (3 h) or subacutely (3 wk) before intratracheal instillation of LPS and ALI was assessed 18 h after LPS administration by measuring lung static compliance, lung edema, vascular permeability, inflammation, and alveolar apoptosis. We found that as little as 3 h of exposure to CS enhanced LPS-induced ALI in both strains of mice. Similar exacerbating effects were observed after 3 wk of preexposure to CS. However, there w...
Source: AJP: Lung Cellular and Molecular Physiology - December 31, 2016 Category: Respiratory Medicine Authors: Sakhatskyy, P., Wang, Z., Borgas, D., Lomas-Neira, J., Chen, Y., Ayala, A., Rounds, S., Lu, Q. Tags: RESEARCH ARTICLE Source Type: research

Toll-like receptor 4 activation attenuates profibrotic response in control lung fibroblasts but not in fibroblasts from patients with IPF
Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease with a median survival of 3 yr. IPF deteriorates upon viral or bacterial lung infection although pulmonary infection (pneumonia) in healthy lungs rarely induces fibrosis. Bacterial lipopolysaccharide (LPS) activates Toll-like receptor 4 (TLR4), initiating proinflammatory pathways. As TLR4 has already been linked to hepatic fibrosis and scleroderma, we now investigated the role of TLR4 in IPF fibroblasts. Lung tissue sections from patients with IPF were analyzed for TLR4 expression. Isolated normal human lung fibroblasts (NL-FB) and IPF fibroblasts (IPF-FB) w...
Source: AJP: Lung Cellular and Molecular Physiology - December 31, 2016 Category: Respiratory Medicine Authors: Ebener, S., Barnowski, S., Wotzkow, C., Marti, T. M., Lopez-Rodriguez, E., Crestani, B., Blank, F., Schmid, R. A., Geiser, T., Funke, M. Tags: RESEARCH ARTICLE Source Type: research

Effectiveness of individualized lung recruitment strategies at birth: an experimental study in preterm lambs
Respiratory transition at birth involves rapidly clearing fetal lung liquid and preventing efflux back into the lung while aeration is established. We have developed a sustained inflation (SIOPT) individualized to volume response and a dynamic tidal positive end-expiratory pressure (PEEP) (open lung volume, OLV) strategy that both enhance this process. We aimed to compare the effect of each with a group managed with PEEP of 8 cmH2O and no recruitment maneuver (No-RM), on gas exchange, lung mechanics, spatiotemporal aeration, and lung injury in 127 ± 1 day preterm lambs. Forty-eight fetal-instrumented lambs exposed t...
Source: AJP: Lung Cellular and Molecular Physiology - December 31, 2016 Category: Respiratory Medicine Authors: Tingay, D. G., Rajapaksa, A., Zannin, E., Pereira-Fantini, P. M., Dellaca, R. L., Perkins, E. J., Zonneveld, C. E. E., Adler, A., Black, D., Frerichs, I., Lavizzari, A., Sourial, M., Grychtol, B., Mosca, F., Davis, P. G. Tags: RESEARCH ARTICLE Source Type: research

Transforming growth factor-{beta} plays divergent roles in modulating vascular remodeling, inflammation, and pulmonary fibrosis in a murine model of scleroderma
In this study we analyzed how blocking TGFβ signaling affects pulmonary abnormalities in Fos-related antigen 2 (Fra-2) transgenic (Tg) mice, a murine model that manifests three important lung pathological features of SSc: fibrosis, inflammation, and vascular remodeling. To interrupt TGFβ signaling in the Fra-2 Tg mice, we used a pan-TGFβ-blocking antibody, 1D11, and Tg mice in which TGFβ receptor type 2 (Tgfbr2) is deleted from smooth muscle cells and myofibroblasts (α-SMA-CreER;Tgfbr2flox/flox). Global inhibition of TGFβ by 1D11 did not ameliorate lung fibrosis histologically or biochemicall...
Source: AJP: Lung Cellular and Molecular Physiology - December 31, 2016 Category: Respiratory Medicine Authors: Tsujino, K., Reed, N. I., Atakilit, A., Ren, X., Sheppard, D. Tags: RESEARCH ARTICLE Source Type: research

IL-23 secreted by bronchial epithelial cells contributes to allergic sensitization in asthma model: role of IL-23 secreted by bronchial epithelial cells
In conclusion, IL-23 is another important bronchial epithelial cell-driven cytokine which may contribute to the development of house dust mite allergic sensitization and asthma. (Source: AJP: Lung Cellular and Molecular Physiology)
Source: AJP: Lung Cellular and Molecular Physiology - December 31, 2016 Category: Respiratory Medicine Authors: Lee, H. S., Park, D.-E., Lee, J.-W., Chang, Y., Kim, H. Y., Song, W.-J., Kang, H.-R., Park, H.-W., Chang, Y.-S., Cho, S.-H. Tags: RESEARCH ARTICLE Source Type: research

Aging exacerbates acute lung injury-induced changes of the air-blood barrier, lung function, and inflammation in the mouse
Acute lung injury (ALI) is characterized by hypoxemia, enhanced permeability of the air-blood barrier, and pulmonary edema. Particularly in the elderly, ALI is associated with increased morbidity and mortality. The reasons for this, however, are poorly understood. We hypothesized that age-related changes in pulmonary structure, function, and inflammation lead to a worse prognosis in ALI. ALI was induced in young (10 wk old) and old (18 mo old) male C57BL/6 mice by intranasal application of 2.5 mg lipopolysaccharide (LPS)/kg body wt or saline (control mice). After 24 h, lung function was assessed, and lungs were either proc...
Source: AJP: Lung Cellular and Molecular Physiology - December 31, 2016 Category: Respiratory Medicine Authors: Kling, K. M., Lopez-Rodriguez, E., Pfarrer, C., Mühlfeld, C., Brandenberger, C. Tags: RESEARCH ARTICLE Source Type: research

Gene expression profiling of epigenetic chromatin modification enzymes and histone marks by cigarette smoke: implications for COPD and lung cancer
Chromatin-modifying enzymes mediate DNA methylation and histone modifications on recruitment to specific target gene loci in response to various stimuli. The key enzymes that regulate chromatin accessibility for maintenance of modifications in DNA and histones, and for modulation of gene expression patterns in response to cigarette smoke (CS), are not known. We hypothesize that CS exposure alters the gene expression patterns of chromatin-modifying enzymes, which then affects multiple downstream pathways involved in the response to CS. We have, therefore, analyzed chromatin-modifying enzyme profiles and validated by quantit...
Source: AJP: Lung Cellular and Molecular Physiology - December 11, 2016 Category: Respiratory Medicine Authors: Sundar, I. K., Rahman, I. Tags: ARTICLES Source Type: research

Age and testosterone mediate influenza pathogenesis in male mice
Influenza severity increases with age, with hospitalization and mortality rates during seasonal influenza epidemics being higher in older men than age-matched women. As it is known that with age, circulating testosterone levels decline in males, we hypothesized that reduced testosterone contributes to age-associated increases in influenza severity. A murine model was used to test this hypothesis. As in men, testosterone concentrations were lower in aged (18 mo) than young (2 mo) male C57BL/6 mice. Following inoculation with influenza A virus (IAV), aged males experienced greater morbidity, clinical disease, and pulmonary i...
Source: AJP: Lung Cellular and Molecular Physiology - December 11, 2016 Category: Respiratory Medicine Authors: vom Steeg, L. G., Vermillion, M. S., Hall, O. J., Alam, O., McFarland, R., Chen, H., Zirkin, B., Klein, S. L. Tags: ARTICLES Source Type: research

Dung biomass smoke activates inflammatory signaling pathways in human small airway epithelial cells
Animal dung is a biomass fuel burned by vulnerable populations who cannot afford cleaner sources of energy, such as wood and gas, for cooking and heating their homes. Exposure to biomass smoke is the leading environmental risk for mortality, with over 4,000,000 deaths each year worldwide attributed to indoor air pollution from biomass smoke. Biomass smoke inhalation is epidemiologically associated with pulmonary diseases, including chronic obstructive pulmonary disease (COPD), lung cancer, and respiratory infections, especially in low and middle-income countries. Yet, few studies have examined the mechanisms of dung biomas...
Source: AJP: Lung Cellular and Molecular Physiology - December 11, 2016 Category: Respiratory Medicine Authors: McCarthy, C. E., Duffney, P. F., Gelein, R., Thatcher, T. H., Elder, A., Phipps, R. P., Sime, P. J. Tags: ARTICLES Source Type: research

Soluble epoxide hydrolase deficiency or inhibition enhances murine hypoxic pulmonary vasoconstriction after lipopolysaccharide challenge
Hypoxic pulmonary vasoconstriction (HPV) is the response of the pulmonary vasculature to low levels of alveolar oxygen. HPV improves systemic arterial oxygenation by matching pulmonary perfusion to ventilation during alveolar hypoxia and is impaired in lung diseases such as the acute respiratory distress syndrome (ARDS) and in experimental models of endotoxemia. Epoxyeicosatrienoic acids (EETs) are pulmonary vasoconstrictors, which are metabolized to less vasoactive dihydroxyeicosatrienoic acids (DHETs) by soluble epoxide hydrolase (sEH). We hypothesized that pharmacological inhibition or a congenital deficiency of sEH in ...
Source: AJP: Lung Cellular and Molecular Physiology - December 11, 2016 Category: Respiratory Medicine Authors: Wepler, M., Beloiartsev, A., Buswell, M. D., Panigrahy, D., Malhotra, R., Buys, E. S., Radermacher, P., Ichinose, F., Bloch, D. B., Zapol, W. M. Tags: CALL FOR PAPERS Source Type: research