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Lung Epithelium (lung + epithelium)
Selected AbstractsConditional gene inactivation reveals roles for Fgf10 and Fgfr2 in establishing a normal pattern of epithelial branching in the mouse lungDEVELOPMENTAL DYNAMICS, Issue 8 2009Lisa L. Abler Abstract Fibroblast growth factor 10 (FGF10) signaling through FGF receptor 2 (FGFR2) is required for lung initiation. While studies indicate that Fgf10 and Fgfr2 are also important at later stages of lung development, their roles in early branching events remain unclear. We addressed this question through conditional inactivation of both genes in mouse subsequent to lung initiation. Inactivation of Fgf10 in lung mesenchyme resulted in smaller lobes with a reduced number of branches. Inactivation of Fgfr2 in lung epithelium resulted in disruption of lobes and small epithelial outgrowths that arose arbitrarily along the main bronchi. In both mutants, there was an increase in cell death. Also, the expression patterns of key signaling molecules implicated in branching morphogenesis were altered and a proximal lung marker was expanded distally. Our results indicate that both Fgf10 and Fgfr2 are required for a normal branching program and for proper proximal,distal patterning of the lung.Developmental Dynamics 238:1999,2013, 2009. © 2009 Wiley-Liss, Inc. [source] Protein phosphatase 1, is required for murine lung growth and morphogenesisDEVELOPMENTAL DYNAMICS, Issue 4 2004Kadija-Kathy Hormi-Carver Abstract Protein phosphatase 1 (PP1) plays important roles in cell cycle control and apoptosis, two processes that impinge on morphogenesis and differentiation. Following the precedent set by other molecules regulating the cell cycle and apoptosis, we hypothesized that PP1 may have context-specific roles in development. Therefore, we have studied the spatial and temporal expression of PP1, during murine lung development and determined the consequences of loss of PP1, function on branching morphogenesis. By using an immunohistochemical approach, we show here that PP1, was expressed throughout the epithelium and mesenchyme upon the emergence of the lung primordium on embryonic day 10, with immunostaining exclusively extranuclear. During the late pseudoglandular stage, PP1, was predominantly expressed in the distal lung epithelium, whereas the mesenchyme contained very little or no PP1, protein. Peri- and postnatally, PP1, immunostaining was mostly nuclear in apparently differentiated cells, as judged by colocalization with well-known markers for lung differentiation. Exposure of fetal lung explants to antisense oligodeoxynucleotides against PP1,, resulted in decreased overall size of the cultured lung, a defect in forming new airways, lack of expression of surfactant protein C, and histologic signs of poor differentiation. These data suggest that PP1, is required for branching morphogenesis and differentiation. Developmental Dynamics 229:791,801, 2004. © 2004 Wiley-Liss, Inc. [source] Cigarette smoke extract affects functional activity of MRP1 in bronchial epithelial cellsJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 5 2007Margaretha van der Deen Abstract Cigarette smoke is the principal risk factor for development of chronic obstructive pulmonary disease (COPD). Multidrug resistance-associated protein 1 (MRP1) is a member of the ATP-binding cassette (ABC) superfamily of transporters, which transport physiologic and toxic substrates across cell membranes. MRP1 is highly expressed in lung epithelium. This study aims to analyze the effect of cigarette smoke extract (CSE) on MRP1 activity. In the human bronchial epithelial cell line 16HBE14o,, MRP1 function was studied flow cytometrically by cellular retention of carboxyfluorescein (CF) after CSE incubation and MRP1 downregulation by RNA interference (siRNA). Cell survival was measured by the MTT assay. Immunocytochemically, it was shown that 16HBE14o, expressed MRP1 and breast cancer resistance protein. Coincubation of CSE IC50 (1.53% ± 0.22%) with MK571 further decreased cell survival 31% (p, = 0.018). CSE increased cellular CF retention dose dependently from 1.7-fold at 5% CSE to 10.3-fold at 40% CSE (both p < 0.05). siRNA reduced MRP1 RNA expression with 49% and increased CF accumulation 67% versus control transfected cells. CSE exposure further increased CF retention 24% (p = 0.031). A linear positive relation between MRP1 function and CSE-modulating effects (r = 0.99, p =0.089) was shown in untransfected, control transfected, and MRP1 downregulated 16HBE14o, cells analogous to blocking effects with MRP1 inhibitor MK571 (r = 0.99, p = 0.034). In conclusion, cigarette smoke extract affects MRP1 activity probably competitively in bronchial epithelial cells. Inhibition of MRP1 in turn results in higher CSE toxicity. We propose that MRP1 may be a protective protein for COPD development. © 2007 Wiley Periodicals, Inc. J Biochem Mol Toxicol 21:243,251, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20187 [source] Quantitative cytokine gene expression in CF airway,PEDIATRIC PULMONOLOGY, Issue 5 2004Marianne S. Muhlebach MD Abstract Bronchoalveolar lavage fluid (BALF) in cystic fibrosis (CF) shows increased inflammation, which could be due to abnormal cytokine regulation. Bronchial epithelial cells and migratory inflammatory cells produce these cytokines, but few quantitative in vivo data are available comparing young CF patients with controls. We hypothesized that IL-8 mRNA abundance was higher in young CF vs. non-CF disease control patients in lung epithelium and inflammatory cells. Bronchial epithelial cells (BEC) were obtained by brush biopsy, and airway inflammatory cells (BALFC) by bronchoalveolar lavage, in 17 CF and 21 non-CF patients <5 years old undergoing clinically indicated bronchoscopy. Cellular mRNA expression was quantified by real-time PCR and normalized to glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Abundance of IL-8/GAPDH in BEC was significantly higher in CF (14.8,±,3.3) than non-CF (4.2,±,0.6) samples, and this difference was also significant when patients were stratified according to infection. In BALFC, the difference in IL-8 expression did not reach statistical significance: CF (17.1,±,6.5) vs. non-CF (6.8,±,1.9), but BALF cell number/ml was significantly higher in CF. IL-10 mRNA was very low in all samples, without showing a decrease in CF vs. non-CF patients. We conclude that early in the disease, IL-8 mRNA expression in BEC is increased in CF in vivo. Although IL-8 mRNA in migratory cells was not significantly higher in CF, these cells may still contribute to elevated IL-8 in airway secretions, secondary to increased cell density in BALF. Pediatr Pulmonol. 2004; 37:393,399. © 2004 Wiely-Liss, Inc. [source] Ablation of Lung Epithelial Cells Deregulates FGF-10 Expression and Impairs Lung Branching MorphogenesisTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 1 2009Namjin Kim Abstract Epithelial-mesenchymal interactions are essential for tissue patterning during organogenesis. Distal lung epithelium and its adjacent mesenchyme comprise the epithelial-mesenchymal signaling unit that regulates lung branching morphogenesis. Tissue recombination experiments have demonstrated the importance of mesenchymal signals in inducing lung epithelial differentiation and branching, but the role of the epithelium in regulating mesenchymal signals has not been well characterized. Using transgenic mice, we ablated distal lung epithelial cells during lung development by inducing the expression of a constitutively active proapoptotic Bax protein under the surfactant protein C (SP-C) promoter. We found that epithelial cell ablation results in impaired lung branching morphogenesis, which progresses to emphysematous airspaces in the adults. Mesenchymal expression of fibroblast growth factor 10 (Fgf-10), whose strict spatial and temporal expression is critical for proper lung branching morphogenesis, is disrupted and loses its localized pattern. Interestingly, the expression of sonic hedgehog (Shh), an epithelial gene known to modulate Fgf-10 expression, is unchanged, indicating the existence of other distal epithelial signals that regulate mesenchymal Fgf-10expression. We propose that distal SP-C expressing lung epithelial cells provide essential signals for the downregulation of Fgf-10expression in the distal mesenchyme during lung development. 292:123,130, 2009. © 2008 Wiley-Liss, Inc. [source] Chlamydia pneumoniae and atherosclerosisCELLULAR MICROBIOLOGY, Issue 2 2004Robert J. Belland Summary Exposure to Chlamydia pneumoniae is extremely common, and respiratory infections occur repeatedly among most people. Strong associations exist between C. pneumoniae infection and atherosclerosis as demonstrated by: (i) sero-epidemiological studies showing that patients with cardiovascular disease have higher titres of anti- C. pneumoniae antibodies compared with control patients; (ii) detection of the organism within atherosclerotic lesions, but not in adjacent normal tissue by immunohistochemistry, polymerase chain reaction and electron microscopy and by culturing the organism from lesions; and (iii) showing that C. pneumoniae can either initiate lesion development or cause exacerbation of lesions in rabbit and mouse animal models respectively. The association of this organism with atherosclerosis has also provided sufficient impetus to conduct a variety of human secondary prevention antibiotic treatment trials. The results of these studies have been mixed and, thus far, no clear long-lasting benefit has emerged from these types of investigations. Studies of C. pneumoniae pathogenesis have shown that the organism can infect many cell types associated with both respiratory and cardiovascular sites, including lung epithelium and resident alveolar macrophages, circulating monocytes, arterial smooth muscle cells and vascular endothelium. Infected cells have been shown to exhibit characteristics associated with the development of cardiovascular disease (e.g. secretion of proinflammatory cytokines and procoagulants by infected endothelial cells and foam cell formation by infected macrophages). More detailed analysis of C. pneumoniae pathogenesis has been aided by the availability of genomic sequence information. Genomic and proteomic analyses of C. pneumoniae infections in relevant cell types will help to define the pathogenic potential of the organism in both respiratory and cardiovascular disease. [source] Expression of water and ion transporters in tracheal aspirates from neonates with respiratory distressACTA PAEDIATRICA, Issue 11 2009Yanhong Li Abstract Aim:, The aim of the study was to determine whether neonatal respiratory distress is related to changes in water and ion transporter expression in lung epithelium. Methods:, The study included 32 neonates on mechanical ventilation: 6 patients with normal lung X-rays (control group), eight with respiratory distress syndrome (RDS), eight with transient tachypnea of the newborn (TTN), 10 with abnormal lung X-rays (mixed group). The protein abundance of water channel AQP5, epithelial sodium channel (ENaC; ,-, ,- and ,-ENaC) and Na+, K+ -ATPase ,1 were examined in tracheal aspirates using semiquantitative immunoblotting. Results:, ,-ENaC level was significantly lower in RDS group compared with infants with TTN and infants in the control group. AQP5 expression was significantly higher in TTN compared with the infants with RDS and all other infants with abnormal lung X-rays. Conclusion:, Neonatal respiratory distress is associated with changes in ,-ENaC and AQP5 expression. The lower ,-ENaC expression may be one of the factors that predispose to the development of RDS. The higher AQP5 expression may provide the possibility for reabsorption of postnatal lung liquid, which contributes to quick recovery of infants with TTN. [source] | |||||||||||||