Methionine Aminopeptidase-2 as a Selective Target of Myofibroblasts in Pulmonary Fibrosis
Autor: | Alain C. Borczuk, Steven Greenberg, Daniel J. Kass, Robert S. Bridges |
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Rok vydání: | 2007 |
Předmět: |
Pulmonary and Respiratory Medicine
Pathology medicine.medical_specialty Antimetabolites Pulmonary Fibrosis Clinical Biochemistry Lung injury Biology Bleomycin Aminopeptidases Rats Sprague-Dawley Mice Idiopathic pulmonary fibrosis chemistry.chemical_compound Cyclohexanes Pulmonary fibrosis medicine Animals Humans Fumagillin RNA Small Interfering Fibroblast Lung Molecular Biology Antibiotics Antineoplastic Metalloendopeptidases Muscle Smooth Cell Biology Fibroblasts respiratory system medicine.disease METAP2 Rats respiratory tract diseases medicine.anatomical_structure Bromodeoxyuridine chemistry Rats Inbred Lew Fatty Acids Unsaturated Cancer research Intercellular Signaling Peptides and Proteins Female Collagen Sesquiterpenes medicine.drug |
Zdroj: | American Journal of Respiratory Cell and Molecular Biology. 37:193-201 |
ISSN: | 1535-4989 1044-1549 |
Popis: | 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. |
Databáze: | OpenAIRE |
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