Abstract:
:This study investigated whether hypoxia-inducible factor (HIF)-1 influences postnatal vascularization and alveologenesis in mice and whether stable (constitutive-active) HIF could prevent hyperoxia-induced lung injury. We assessed postnatal vessel and alveolar formation in transgenic mice, expressing a stable, constitutive-active, HIF1α-subunit (HIF-1αΔODD) in the distal lung epithelium. In addition, we compared lung function, histology, and morphometry of neonatal transgenic and wild-type mice subjected to hyperoxia. We found that postnatal lungs of HIF-1αΔODD mice had a greater peripheral vessel density and displayed advanced alveolarization compared with control lungs. Stable HIF-1α expression was associated with increased postnatal expression of angiogenic factors, including vascular endothelial growth factor, angiopoietins 1 and 2, Tie2, and Ephrin B2 and B4. Hyperoxia-exposed neonatal HIF-1αΔODD mice exhibited worse lung function but had similar histological and surfactant abnormalities compared with hyperoxia-exposed wild-type controls. In conclusion, expression of constitutive-active HIF-1α in the lung epithelium was associated with increased postnatal vessel growth via up-regulation of angiogenic factors. The increase in postnatal vasculature was accompanied by enhanced alveolar formation. However, stable HIF-1α expression in the distal lung did not prevent hyperoxia-induced lung injury in neonates but instead worsened lung function.
journal_name
Am J Respir Cell Mol Biolauthors
Tibboel J,Groenman FA,Selvaratnam J,Wang J,Tseu I,Huang Z,Caniggia I,Luo D,van Tuyl M,Ackerley C,de Jongste JC,Tibboel D,Post Mdoi
10.1165/rcmb.2014-0037OCsubject
Has Abstractpub_date
2015-04-01 00:00:00pages
448-58issue
4eissn
1044-1549issn
1535-4989journal_volume
52pub_type
杂志文章abstract::The surfactant-associated proteins SP-A and SP-D are members of a family of collagenous host defense lectins, designated collectins. There is increasing evidence that these pulmonary epithelial-derived proteins are important components of the innate immune response to microbial challenge, and that they participate in ...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章,评审
doi:10.1165/ajrcmb.19.2.140
更新日期:1998-08-01 00:00:00
abstract::The hydroxyl radical (.OH) is a highly reactive oxygen free radical that has been implicated as a cause of lung injury following exposure to silica and silicates. Despite evidence that silica generates .OH in vitro, there has been no previous demonstration of in vivo production of .OH after exposure to nonfibrous mine...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.12.2.7865220
更新日期:1995-02-01 00:00:00
abstract::Chronic obstructive pulmonary disease (COPD) is a major disease of the lungs. It primarily occurs after a prolonged period of cigarette smoking. Chronic inflammation of airways and the alveolar space as well as lung tissue destruction are the hallmarks of COPD. Recently it has been shown that cellular senescence might...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章,评审
doi:10.1165/rcmb.2013-0382PS
更新日期:2014-09-01 00:00:00
abstract::The effects of hypoxia on the regulation of inducible nitric oxide synthase (NOS) 2 expression were examined in cultured rat pulmonary microvascular endothelial cells (EC). EC did not express NOS 2 mRNA or protein when exposed to normoxia or hypoxia unless they were pretreated with interleukin (IL)-1beta and/or tumor ...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.26.1.4510
更新日期:2002-01-01 00:00:00
abstract::The lung is richly supplied with peptidergic nerves that store and secrete substance P (SP), vasoactive intestinal peptide (VIP), and other neuropeptides known to potently modulate leukocyte function in vitro and airway inflammation in vivo. To investigate and characterize neuromodulation of immune responses compartme...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.16.2.9032120
更新日期:1997-02-01 00:00:00
abstract::In the present study, splenic dendritic cells (DC) and alveolar macrophages (AM) were pulsed with antigen in vitro and subsequently intratracheally instilled to test whether these cells have the capacity to sensitize T cells in the draining lymph nodes of the lung. The data demonstrate that antigen-pulsed DC, instille...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb/8.3.319
更新日期:1993-03-01 00:00:00
abstract::Monkey Clara cell 10 kDa protein (CC10) was purified from monkey lung lavage. This protein showed an apparent molecular weight of about 10 kDa and 5 kDa under non-reducing and reducing conditions, respectively, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. From the amino acid sequence dat...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.15.3.8810640
更新日期:1996-09-01 00:00:00
abstract::Hypersensitivity pneumonitis (HP) is an allergic granulomatous interstitial lung disease resulting from a reaction of selected individuals to repeated inhalations of certain antigens. HP is characterized by chronic inflammation, and the development of the disease seems to be immunologically mediated. In farmer's lung,...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb/5.2.198
更新日期:1991-08-01 00:00:00
abstract::Klebsiella pneumoniae is a common cause of pneumonia. Previous studies have documented an important role for Toll-like receptors (TLRs) expressed by myeloid cells in the recognition of K. pneumoniae and the initiation of a protective immune response. Lung epithelial cells also express TLRs and can participate in innat...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2016-0190OC
更新日期:2017-05-01 00:00:00
abstract::At birth, the mammalian lung is still immature. The alveoli are not yet formed and the interairspace walls contain two capillary layers which are separated by an interstitial core. After alveolarization (first 2 postnatal weeks in rats) the alveolar septa mature: their capillary layers merge, the amount of connective ...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.17.3.2737
更新日期:1997-09-01 00:00:00
abstract::The effect of human recombinant stem cell factor (SCF) on inflammatory mediator release and smooth muscle contraction was evaluated in human isolated intralobar bronchi. Bronchi from 21 of 26 donors contracted in response to SCF. The threshold concentration was approximately 0.01 micrograms/ml. At 1 micrograms/ml, the...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.11.6.7524570
更新日期:1994-12-01 00:00:00
abstract::T1alpha is a protein of unknown function that is expressed at the plasma membrane in epithelia involved in fluid transport, including type I alveolar epithelial cells, choroid plexus, and ciliary epithelium. The purpose of this study was to test the hypothesis that T1alpha functions as a water channel or a regulator o...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.19.1.2953
更新日期:1998-07-01 00:00:00
abstract::Endothelin, an endothelium-derived vasoconstrictor peptide, has recently been reported to exist in airway epithelial cells. To elucidate a possible role of endothelin on epithelial functions, we studied the effects of this peptide on ciliary beat frequency (CBF) and electrical properties of canine cultured tracheal ep...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb/4.5.426
更新日期:1991-05-01 00:00:00
abstract::Airway epithelial cells produce a number of chemokines, including eotaxins. Among the three known eotaxins, T helper (Th) type 2 cytokines have been observed to induce the expression of eotaxin-3 mRNA. This study investigated the effect of interferon (IFN)-gamma, a Th1 cytokine, on Th2 cytokine-induced eotaxin-3 produ...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2004-0128OC
更新日期:2004-10-01 00:00:00
abstract::Adenosine is a signaling nucleoside that has been proposed to contribute to the pathogenesis of asthma and chronic obstructive pulmonary disease. Previous studies suggest that adenosine might play an important role in modulating levels of inflammatory mediators in the lung. Because airway epithelium is an important ce...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2005-0476OC
更新日期:2006-11-01 00:00:00
abstract::Obesity affects the incidence and severity of asthma in at least two major phenotypes: an early-onset allergic (EOA) form that is complicated by obesity and a late-onset nonallergic (LONA) form that occurs only in the setting of obesity. Both groups exhibit airway hyperresponsiveness to methacholine challenge but exhi...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章,评审
doi:10.1165/rcmb.2016-0019PS
更新日期:2016-05-01 00:00:00
abstract::Sox2, a transcription factor critical for the maintenance of embryonic stem cells and induction of pluripotent stem cells, is expressed exclusively in the conducting airway epithelium of the lung, where it is required for differentiation of nonciliated, goblet, and ciliated cells. To determine the role of Sox2 in resp...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2010-0149OC
更新日期:2011-07-01 00:00:00
abstract::MyD88 is an adapter protein required for the induction of proinflammatory cytokines by most Toll-like receptors (TLR), and Pseudomonas aeruginosa expresses ligands for multiple TLRs. MyD88(-/-) (KO) mice are highly susceptible to aerosolized P. aeruginosa, failing to elicit an early inflammatory response and permittin...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2005-0199OC
更新日期:2005-11-01 00:00:00
abstract::Lung development is associated with a surge in surfactant phosphatidylcholine (PC) production to prepare the newborn for extrauterine breathing. This process is associated with a marked increase in the activity of the rate-regulatory surfactant enzyme, CTP:phosphocholine cytidylyltransferase (CCTalpha). To investigate...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2005-0401OC
更新日期:2006-09-01 00:00:00
abstract::Alveolar hypoxia produces widespread systemic inflammation in rats. The inflammation appears to be triggered by activation of mast cells by a mediator released from alveolar macrophages, not by the reduced systemic partial pressure of oxygen (PO2). If this is correct, the following should apply: (1) neither mast cells...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2008-0417OC
更新日期:2009-11-01 00:00:00
abstract::Bleomycin-induced lung disease is characterized by cell injury followed by fibroblast proliferation. Cells respond to injury by synthesizing a family of heat shock proteins. These proteins are critical to cell survival, and those of the 70,000 MW group (hsp 70) are essential for cell division and proliferation. To eva...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb/1.2.89
更新日期:1989-08-01 00:00:00
abstract::IL-15 has recently been shown to induce the differentiation of functional dendritic cells (DCs) from human peripheral blood monocytes. Since DCs lay in close proximity to epithelial cells in the airway mucosa, we investigated whether airway epithelial cells release IL-15 in response to inflammatory stimuli and thereby...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2006-0235OC
更新日期:2007-07-01 00:00:00
abstract::Wheeze is a common symptom in infants, but not all wheezers develop asthma. Indeed, up to 50% of wheezing children outgrow their symptoms by school age. How to predict if early wheeze will become asthma is still a matter of vivid debate. In this work, we sought to assess the clinical and pathological factors that migh...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2018-0009OC
更新日期:2018-10-01 00:00:00
abstract::The glucocorticoids (GC) and retinoids (RA) modulate branching morphogenesis and cytodifferentiation in the developing lung. We investigated downstream target genes that link glucocorticoid stimulation to the achievement of a mature lung in glucocorticoid receptor (GR) knockout mice. All GR(null) mice and approximatel...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2002-0047oc
更新日期:2003-01-01 00:00:00
abstract::Surfactant is an apically-secreted surface-active material containing primarily disaturated phosphatidylcholine (DSPtdCho) that is released from alveolar epithelia into the alveolus. Surfactant deficiency is an important aspect of inflammatory lung disease and may result from extravasation of serum lipoproteins into t...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2004-0038OC
更新日期:2004-08-01 00:00:00
abstract::Airway epithelial cells cultured at the air-liquid interface possess highly differentiated functions and structures compared with the cells cultured under immersion. We examined the oxidative metabolism and glycolysis in cow tracheal epithelial cells on Days 3, 6, 10, and 13, cultured under three different conditions:...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.16.1.8998080
更新日期:1997-01-01 00:00:00
abstract::We have developed a method to harvest and culture Clara cells isolated from guinea pig lungs. Their identity was confirmed by the presence of CC16kD protein specific for these cells; we studied their capacity to generate endothelin 1 (ET-1). Using monoclonal antibody and immunofluorescence techniques, ET-1 was localiz...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.14.4.8600940
更新日期:1996-04-01 00:00:00
abstract::Notch is an ancient cell-signaling system that regulates the specification of cell fate. This study examined the role of Notch in the epithelial-mesenchymal transition (EMT) and myofibroblast differentiation of cultured RLE-6TN cells (i.e., rat alveolar epithelial cells). The activation of Notch, either by ectopic exp...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2010-0140oc
更新日期:2011-07-01 00:00:00
abstract::Mutations in the p53 gene have been implicated to play an important role in the development of various human cancers. To evaluate the importance of p53 in lung cancer, a transgenic mouse model was established by utilizing the Clara cell secretory protein (CCSP) promoter to target the expression of a dominant-negative ...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.27.2.4799
更新日期:2002-08-01 00:00:00
abstract::Smoking cigarettes is the major risk factor for chronic obstructive pulmonary disease (COPD). COPD is a condition associated with chronic pulmonary inflammation, characterized by macrophage activation, neutrophil recruitment, and cell injury. Many substances contained in cigarette smoke, including reactive oxygen spec...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2007-0130OC
更新日期:2007-11-01 00:00:00