title: Modeling pulmonary fibrosis by abnormal expression of telomerase/apoptosis/collagen V in experimental usual interstitial pneumonia.
abstract: Limitations on tissue proliferation capacity determined by telomerase/apoptosis balance have been implicated in pathogenesis of idiopathic pulmonary fibrosis. In addition, collagen V shows promise as an inductor of apoptosis. We evaluated the quantitative relationship between the telomerase/apoptosis index, collagen V synthesis, and epithelial/fibroblast replication in mice exposed to butylated hydroxytoluene (BHT) at high oxygen concentration. Two groups of mice were analyzed: 20 mice received BHT, and 10 control mice received corn oil. Telomerase expression, apoptosis, collagen I, III, and V fibers, and hydroxyproline were evaluated by immunohistochemistry, in situ detection of apoptosis, electron microscopy, immunofluorescence, and histomorphometry. Electron microscopy confirmed the presence of increased alveolar epithelial cells type 1 (AEC1) in apoptosis. Immunostaining showed increased nuclear expression of telomerase in AEC type 2 (AEC2) between normal and chronic scarring areas of usual interstitial pneumonia (UIP). Control lungs and normal areas from UIP lungs showed weak green birefringence of type I and III collagens in the alveolar wall and type V collagen in the basement membrane of alveolar capillaries. The increase in collagen V was greater than collagens I and III in scarring areas of UIP. A significant direct association was found between collagen V and AEC2 apoptosis. We concluded that telomerase, collagen V fiber density, and apoptosis evaluation in experimental UIP offers the potential to control reepithelization of alveolar septa and fibroblast proliferation. Strategies aimed at preventing high rates of collagen V synthesis, or local responses to high rates of cell apoptosis, may have a significant impact in pulmonary fibrosis.
authors.affiliation: Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil.
authors.forename: E R
authors.initials: ER
authors.lastname: Parra
authors.affiliation: Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil.
authors.forename: M S
authors.initials: MS
authors.lastname: Pincelli
authors.affiliation: Disciplina de Reumatologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil.
authors.forename: W R
authors.initials: WR
authors.lastname: Teodoro
authors.affiliation: Disciplina de Reumatologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil.
authors.forename: A P P
authors.initials: AP
authors.lastname: Velosa
authors.affiliation: Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil.
authors.forename: V
authors.initials: V
authors.lastname: Martins
authors.affiliation: Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil.
authors.forename: M P
authors.initials: MP
authors.lastname: Rangel
authors.affiliation: Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil.
authors.forename: J V
authors.initials: JV
authors.lastname: Barbas-Filho
authors.affiliation: Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil.
authors.forename: V L
authors.initials: VL
authors.lastname: Capelozzi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002084:Butylated Hydroxytoluene; D049109:Cell Proliferation; D024042:Collagen Type I / Q000032:analysis; D024043:Collagen Type II / Q000032:analysis; D024062:Collagen Type V / Q000032:analysis / Q000096:biosynthesis*; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D005455:Fluorescent Antibody Technique; D006909:Hydroxyproline / Q000032:analysis; D054990:Idiopathic Pulmonary Fibrosis / Q000473:pathology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D011650:Pulmonary Alveoli / Q000473:pathology / Q000648:ultrastructure; D011658:Pulmonary Fibrosis / Q000473:pathology*; D013194:Staining and Labeling; D019098:Telomerase / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: D024042:Collagen Type I; D024043:Collagen Type II; D024062:Collagen Type V; D002084:Butylated Hydroxytoluene; D019098:Telomerase; D006909:Hydroxyproline