Methionine aminopeptidase-2 as a selective target of myofibroblasts in pulmonary fibrosis.

Abstract:

:Idiopathic pulmonary fibrosis (IPF) is a progressive, scarring lung disease characterized by fibroblast accumulation and deposition of collagen. Factors that promote growth and/or survival of fibroblasts are potential therapeutic targets. Methionine aminopeptidase 2 (MetAP2), a member of the aminopeptidase family of proteases, has been implicated in cell proliferation in a variety of cell types, but its expression and function in the lung is not known. By immunohistochemistry, MetAP2 was expressed in many cell types, including fibroblasts, in IPF lungs. Fumagillin, an irreversible inhibitor of the enzymatic activity of MetAP2, attenuated collagen deposition in the bleomycin model of acute lung injury in mice. Treatment with fumagillin caused a selective reduction in the numbers of bromodeoxyuridine (BrdU)-positive myofibroblasts, but not type II alveolar epithelial cells, macrophages, or B- and T-lymphocytes in the lungs of bleomycin-treated mice. Incubation of primary rat lung fibroblasts with either fumagillin or with short interfering RNA that targeted MetAP2 led to reduced proliferation, as assessed by incorporation of BrdU. The profibrotic growth factor, platelet-derived growth factor, increased expression of MetAP2 in rat lung fibroblasts. We propose that MetAP2 plays a role in the proliferation of fibroblasts and myofibroblasts in fibrotic lung diseases and may serve as a novel pharmacologic target in IPF.

authors

Kass D,Bridges RS,Borczuk A,Greenberg S

doi

10.1165/rcmb.2006-0352OC

subject

Has Abstract

pub_date

2007-08-01 00:00:00

pages

193-201

issue

2

eissn

1044-1549

issn

1535-4989

pii

2006-0352OC

journal_volume

37

pub_type

杂志文章
  • Surfactant protein-D, a mediator of innate lung immunity, alters the products of nitric oxide metabolism.

    abstract::Surfactant protein (SP)-D, a 43-kD multifunctional collagen-like lectin, is synthesized and secreted by the airway epithelium. SP-D knockout (SP-D [-/-]) mice exhibit an increase in the number and size of airway macrophages, peribronchiolar inflammation, increases in metalloproteinase activity, and development of emph...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2003-0091OC

    authors: Atochina EN,Beers MF,Hawgood S,Poulain F,Davis C,Fusaro T,Gow AJ

    更新日期:2004-03-01 00:00:00

  • Ablation of Pericyte-Like Cells in Lungs by Oropharyngeal Aspiration of Diphtheria Toxin.

    abstract::We demonstrated previously that FoxD1-derived cells in the lung are enriched in pericyte-like cells in mouse lung. These cells express the common pericyte markers and are located adjacent to endothelial cells. In this study, we demonstrate the feasibility of administering diphtheria toxin (DT) by oropharyngeal aspirat...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2016-0083MA

    authors: Hung CF,Chow YH,Liles WC,Altemeier WA,Schnapp LM

    更新日期:2017-02-01 00:00:00

  • Effects of nitric oxide synthases in chronic allergic airway inflammation and remodeling.

    abstract::The precise role of each nitric oxide (NO) synthase (NOS) isoform in the pathobiology of asthma is not well established. Our objective was to investigate the contribution of constitutive NO synthase (cNOS) and inducible NOS (iNOS) isoforms to lung mechanics and inflammatory and remodeling responses in an experimental ...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2005-0391OC

    authors: Prado CM,Leick-Maldonado EA,Yano L,Leme AS,Capelozzi VL,Martins MA,Tibério IF

    更新日期:2006-10-01 00:00:00

  • Age-Dependent Changes in AMPK Metabolic Pathways in the Lung in a Mouse Model of Hemorrhagic Shock.

    abstract::The development of multiple organ failure in patients with hemorrhagic shock is significantly influenced by patient age. Adenosine monophosphate-activated protein kinase (AMPK) is a crucial regulator of energy homeostasis, which coordinates metabolic repair during cellular stress. We investigated whether AMPK-regulate...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2016-0118OC

    authors: Klingbeil LR,Kim P,Piraino G,O'Connor M,Hake PW,Wolfe V,Zingarelli B

    更新日期:2017-05-01 00:00:00

  • An essential role for non-bone marrow-derived cells in control of Pseudomonas aeruginosa pneumonia.

    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

    authors: Hajjar AM,Harowicz H,Liggitt HD,Fink PJ,Wilson CB,Skerrett SJ

    更新日期:2005-11-01 00:00:00

  • Angiotensin-converting enzyme 2/angiotensin-(1-7)/Mas axis protects against lung fibrosis by inhibiting the MAPK/NF-κB pathway.

    abstract::Accumulating evidence has demonstrated that up-regulation of the angiotensin (Ang)-converting enzyme (ACE)/AngII/AngII type 1 receptor (AT1R) axis aggravates pulmonary fibrosis. The recently discovered ACE2/Ang-(1-7)/Mas axis, which counteracts the activity of the ACE/AngII/AT1R axis, has been shown to protect against...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2012-0451OC

    authors: Meng Y,Yu CH,Li W,Li T,Luo W,Huang S,Wu PS,Cai SX,Li X

    更新日期:2014-04-01 00:00:00

  • Bleomycin induces the hsp 70 heat shock promoter in cultured cells.

    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

    authors: Moseley PL,York SJ,York J

    更新日期:1989-08-01 00:00:00

  • The integrated stress response in lung disease.

    abstract::Lungs are repeatedly exposed to inhaled toxic insults, such as smoke, diesel exhaust, and microbes, which elicit cellular stress responses. The phosphorylation of eukaryotic translation initiation factor 2α by one of four stress-sensing kinases triggers a pathway called the integrated stress response that helps protec...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章,评审

    doi:10.1165/rcmb.2014-0019TR

    authors: van 't Wout EF,Hiemstra PS,Marciniak SJ

    更新日期:2014-06-01 00:00:00

  • Genetic ablation of the fpr1 gene confers protection from smoking-induced lung emphysema in mice.

    abstract::Cigarette smoke (CS) is the main causative factor of chronic obstructive pulmonary disease (COPD). Current research supports the concept that airway inflammation is central to the development and progression of the disease. Studies have demonstrated that neutrophils are increased in COPD lungs and that neutrophil-asso...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2012-0036OC

    authors: Cardini S,Dalli J,Fineschi S,Perretti M,Lungarella G,Lucattelli M

    更新日期:2012-09-01 00:00:00

  • Bone marrow-derived mesenchymal stem cells in repair of the injured lung.

    abstract::We sought to determine whether an intact bone marrow is essential to lung repair following bleomycin-induced lung injury in mice, and the mechanisms of any protective effects conferred by bone marrow-derived mesenchymal stem cell (BMDMSC) transfer. We found that myelosupression increased susceptibility to bleomycin in...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2004-0330OC

    authors: Rojas M,Xu J,Woods CR,Mora AL,Spears W,Roman J,Brigham KL

    更新日期:2005-08-01 00:00:00

  • PKR regulates TLR2/TLR4-dependent signaling in murine alveolar macrophages.

    abstract::The double-stranded RNA (dsRNA)-activated serine/threonine kinase R (PKR) is well characterized as an essential component of the innate antiviral response. Recently, PKR has been implicated in Toll-like receptor (TLR) signal transduction in response to bacterial cell wall components. Its contribution to pulmonary immu...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2007-0010OC

    authors: Cabanski M,Steinmüller M,Marsh LM,Surdziel E,Seeger W,Lohmeyer J

    更新日期:2008-01-01 00:00:00

  • Subacute TGFβ Exposure Drives Airway Hyperresponsiveness in Cystic Fibrosis Mice through the PI3K Pathway.

    abstract::Cystic fibrosis (CF) is a lethal genetic disease characterized by progressive lung damage and airway obstruction. The majority of patients demonstrate airway hyperresponsiveness (AHR), which is associated with more rapid lung function decline. Recent studies in the neonatal CF pig demonstrated airway smooth muscle (AS...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2019-0158OC

    authors: Kramer EL,Madala SK,Hudock KM,Davidson C,Clancy JP

    更新日期:2020-05-01 00:00:00

  • Expression of a novel high molecular-weight myosin light chain kinase in endothelium.

    abstract::Myosin light chain phosphorylation results in cellular contraction and is a critical component of agonist-mediated endothelial cell (EC) junctional gap formation and permeability. We have shown that this reaction is catalyzed by a novel high molecular-weight Ca2+/calmodulin-dependent nonmuscle myosin light chain kinas...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.19.5.3125

    authors: Verin AD,Lazar V,Torry RJ,Labarrere CA,Patterson CE,Garcia JG

    更新日期:1998-11-01 00:00:00

  • The antimicrobial/elastase inhibitor elafin regulates lung dendritic cells and adaptive immunity.

    abstract::Infections with bacteria and viruses such as adenovirus are a feature of chronic lung diseases such as chronic obstructive pulmonary diseases (COPD), and may be instrumental in the generation of disease exacerbations. We have previously shown in acute models that elafin (a lung natural chemotactic molecule for macroph...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2005-0405OC

    authors: Roghanian A,Williams SE,Sheldrake TA,Brown TI,Oberheim K,Xing Z,Howie SE,Sallenave JM

    更新日期:2006-05-01 00:00:00

  • Microparticulate Caspase 1 Regulates Gasdermin D and Pulmonary Vascular Endothelial Cell Injury.

    abstract::Lung endothelial cell apoptosis and injury occur throughout all stages of acute lung injury/acute respiratory distress syndrome and impact disease progression. Caspases 1, 4, and 5 are essential for completion of the apoptotic program known as pyroptosis that also involves proinflammatory cytokines. Because gasdermin ...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2017-0393OC

    authors: Mitra S,Exline M,Habyarimana F,Gavrilin MA,Baker PJ,Masters SL,Wewers MD,Sarkar A

    更新日期:2018-07-01 00:00:00

  • Vascular endothelial growth factor receptor 2 blockade disrupts postnatal lung development.

    abstract::Vascular endothelial growth factor (VEGF) is necessary for normal postnatal lung development and may underlie the structural lung damage that follows hyperoxic exposure. To determine the individual roles of VEGF receptors (VEGFR) 2 and 1 on postnatal lung growth, neonatal mice were treated with neutralizing antibodies...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2004-0287OC

    authors: McGrath-Morrow SA,Cho C,Cho C,Zhen L,Hicklin DJ,Tuder RM

    更新日期:2005-05-01 00:00:00

  • Pneumocystis carinii expresses an active Rtt109 histone acetyltransferase.

    abstract::Species in the genus Pneumocystis can cause severe pneumonia in immune-compromised hosts. The identification of specific targets present in Pneumocystis species, but lacking in mammalian hosts, is paramount to developing new means to treat this infection. One such potential protein is Rtt109, which is a type of histon...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2009-0443OC

    authors: Kottom TJ,Han J,Zhang Z,Limper AH

    更新日期:2011-06-01 00:00:00

  • Mechanisms of neutrophil accumulation in the lungs against bacteria.

    abstract::Bacterial lung diseases are a major cause of morbidity and mortality both in immunocompromised and in immunocompetent individuals. Neutrophil accumulation, a pathological hallmark of bacterial diseases, is critical to host defense, but may also cause acute lung injury/acute respiratory distress syndrome. Toll-like rec...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章,评审

    doi:10.1165/rcmb.2009-0047TR

    authors: Balamayooran G,Batra S,Fessler MB,Happel KI,Jeyaseelan S

    更新日期:2010-07-01 00:00:00

  • Enhanced expression of GM-CSF in differentiating eosinophils of atopic and atopic asthmatic subjects.

    abstract::Higher numbers of eosinophil/basophil colony-forming units (Eo/B CFU) are observed in blood of atopic individuals, and can be enhanced in atopic asthmatics by allergen-inhalation challenge. It is known that mature basophils and eosinophils synthesize cytokines relevant to allergic inflammation. To investigate the pote...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.19.1.2871

    authors: Gauvreau GM,O'Byrne PM,Moqbel R,Velazquez J,Watson RM,Howie KJ,Denburg JA

    更新日期:1998-07-01 00:00:00

  • NOX1 Promotes Mesothelial-Mesenchymal Transition Through Modulation of ROS-mediated Signaling.

    abstract::Pleural organization may occur after empyema or complicated parapneumonic effusion and can result in restrictive lung disease with pleural fibrosis (PF). Pleural mesothelial cells; PMCs, may contribute to PF through acquisition of a profibrotic phenotype; meso-mesenchymal transition (MesoMT), which is characterized by...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2020-0077OC

    authors: Qin W,Jeffers A,Owens S,Chauhan P,Komatsu S,Qian G,Guo X,Ikebe M,Idell S,Tucker TA

    更新日期:2021-01-29 00:00:00

  • Genetic Variation along the Histamine Pathway in Children with Allergic versus Nonallergic Asthma.

    abstract::Histamine is an important mediator in the pathogenesis of asthma. Variation in genes along the histamine production, response, and degradation pathway may be important in predicting response to antihistamines. We hypothesize that differences exist among single-nucleotide polymorphisms (SNPs) in genes of the histamine ...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2014-0493OC

    authors: Anvari S,Vyhlidal CA,Dai H,Jones BL

    更新日期:2015-12-01 00:00:00

  • Hydrogen sulfide inhibits proliferation and release of IL-8 from human airway smooth muscle cells.

    abstract::Hydrogen sulfide (H(2)S) is synthesized intracellularly by the enzymes cystathionine-γ-lyase and cystathionine-β-synthase (CBS), and is proposed to be a gasotransmitter with effects in modulating inflammation and cellular proliferation. We determined a role of H(2)S in airway smooth muscle (ASM) function. ASM were rem...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2010-0304OC

    authors: Perry MM,Hui CK,Whiteman M,Wood ME,Adcock I,Kirkham P,Michaeloudes C,Chung KF

    更新日期:2011-10-01 00:00:00

  • Reversible or irreversible remodeling in pulmonary arterial hypertension.

    abstract::Vascular remodeling is an important pathological feature of pulmonary arterial hypertension (PAH), which leads to increased pulmonary vascular resistance, with marked proliferation of pulmonary artery smooth muscle cells (SMC) and/or endothelial cells (EC). Successful treatment of experimental PAH with a platelet-deri...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章,评审

    doi:10.1165/rcmb.2009-0389TR

    authors: Sakao S,Tatsumi K,Voelkel NF

    更新日期:2010-12-01 00:00:00

  • Priming of allergic immune responses by repeated ozone exposure in mice.

    abstract::The effects of repeated ozone exposures on the development of immune responses toward ovalbumin (OVA) were investigated in BALB/c and C57BL/6 mice. Ozone exposures (180 to 500 microg/m(3); 4 h, three times/wk for 4 wk) were combined with a protocol of OVA-aerosol exposure (1% OVA). Immediate cutaneous hypersensitivity...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.23.2.3898

    authors: Neuhaus-Steinmetz U,Uffhausen F,Herz U,Renz H

    更新日期:2000-08-01 00:00:00

  • Heme oxygenase-1: the "emerging molecule" has arrived.

    abstract::Organisms on our planet have evolved in an oxidizing environment that is intrinsically inimical to life, and cells have been forced to devise means of protecting themselves. One of the defenses used most widely in nature is the enzyme heme oxygenase-1 (HO-1). This enzyme performs the seemingly lackluster function of c...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章,评审

    doi:10.1165/ajrcmb.27.1.4862

    authors: Morse D,Choi AM

    更新日期:2002-07-01 00:00:00

  • Heterogeneity of clara cell glutathione. A possible basis for differences in cellular responses to pulmonary cytotoxicants.

    abstract::Clara-cell populations show a high degree of variation in susceptibility to injury by bioactivated cytotoxicants. Because glutathione (GSH) is critical for detoxification of electrophilic metabolites, heterogeneity in Clara cell GSH levels may lead to a wide range of cytotoxic responses. This study was designed to def...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.23.1.3907

    authors: West JA,Chichester CH,Buckpitt AR,Tyler NK,Brennan P,Helton C,Plopper CG

    更新日期:2000-07-01 00:00:00

  • Modulation of deltaF508 cystic fibrosis transmembrane regulator trafficking and function with 4-phenylbutyrate and flavonoids.

    abstract::Over 70% of patients with cystic fibrosis have the DeltaF508 mutation. This protein is a partially functional chloride (Cl-) channel that is prematurely degraded in the endoplasmic reticulum. Specific members of the flavonoid class of compounds have been shown to increase Cl- conductance of wild-type and DeltaF508 cys...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2002-0086OC

    authors: Lim M,McKenzie K,Floyd AD,Kwon E,Zeitlin PL

    更新日期:2004-09-01 00:00:00

  • Inhalation of Stachybotrys chartarum Fragments Induces Pulmonary Arterial Remodeling.

    abstract::Stachybotrys chartarum is a fungal contaminant within the built environment and a respiratory health concern in the United States. The objective of this study was to characterize the mechanisms influencing pulmonary immune responses to repeatedly inhaled S. chartarum. Groups of B6C3F1/N mice repeatedly inhaled viable ...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2019-0221OC

    authors: Croston TL,Lemons AR,Barnes MA,Goldsmith WT,Orandle MS,Nayak AP,Germolec DR,Green BJ,Beezhold DH

    更新日期:2020-05-01 00:00:00

  • Peroxisome Proliferator-Activated Receptor γ Regulates Chronic Alcohol-Induced Alveolar Macrophage Dysfunction.

    abstract::Peroxisome proliferator-activated receptor (PPAR) γ is critical for alveolar macrophage (AM) function. Chronic alcohol abuse causes AM phagocytic dysfunction and susceptibility to respiratory infections by stimulating nicotinamide adenine dinucleotide oxidases (Nox), transforming growth factor-β1, and oxidative stress...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2015-0077OC

    authors: Yeligar SM,Mehta AJ,Harris FL,Brown LA,Hart CM

    更新日期:2016-07-01 00:00:00

  • Leukocyte elastase induces lung epithelial apoptosis via a PAR-1-, NF-kappaB-, and p53-dependent pathway.

    abstract::Leukocyte elastase induces apoptosis of lung epithelial cells via alterations in mitochondrial permeability, but the signaling pathways regulating this response remain uncertain. Here we investigated the involvement of proteinase-activated receptor-1 (PAR-1), the transcription factor NF-kappaB, and the protooncogene p...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2008-0157OC

    authors: Suzuki T,Yamashita C,Zemans RL,Briones N,Van Linden A,Downey GP

    更新日期:2009-12-01 00:00:00