Modeling pulmonary fibrosis by abnormal expression of telomerase/apoptosis/collagen V in experimental usual interstitial pneumonia

• Published in: Brazilian journal of medical and biological research Vol. 47; no. 7; pp. 567 - 575
• Main Authors: Parra, E R, Pincelli, M S, Teodoro, W R, Velosa, A P P, Martins, V, Rangel, M P, Barbas-Filho, J V, Capelozzi, V L
• Format: Journal Article
• Language: English
• Published: Brazil Associacao Brasileira de Divulgacao Cientifica (ABDC) 01-07-2014; Associação Brasileira de Divulgação Científica
• Subjects: Alveolar epithelial cell apoptosis; Animals; Apoptosis; Apoptosis - physiology; BHT experimental model; BIOLOGY; Butylated Hydroxytoluene; Cell Proliferation; Clinical Investigation; Collagen Type I - analysis; Collagen Type II - analysis; Collagen Type V - analysis; Collagen Type V - biosynthesis; Collagen V; Disease Models, Animal; Electron microscopy; Epithelial Cells - metabolism; Epithelial Cells - pathology; Fibroblasts - metabolism; Fibroblasts - pathology; Fluorescent Antibody Technique; Gene expression; Hydroxyproline - analysis; Idiopathic Pulmonary Fibrosis - pathology; Immunohistochemistry; In Situ Nick-End Labeling; Male; MEDICINE, RESEARCH & EXPERIMENTAL; Mice, Inbred BALB C; Microscopy, Electron; Pulmonary Alveoli - pathology; Pulmonary Alveoli - ultrastructure; Pulmonary fibrosis; Pulmonary Fibrosis - pathology; Staining and Labeling; Telomerase; Telomerase - isolation & purification; Telomerase - metabolism; Telomerase activity; Usual interstitial pneumonia; Usual interstitial pneumonia; BHT experimental model; Alveolar epithelial cell apoptosis; Collagen V; Electron microscopy; Telomerase activity
• ISSN: 0100-879X; 1414-431X; 1414-431X
• DOI: 10.1590/1414-431X20143522

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.