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.

Attenuation of lipopolysaccharide-induced lung inflammation by ascorbic acid in rats: Histopathological and ultrastructural study

“…Evident collagen deposition, microphage infiltration and irregularity of the capillary basement membrane indicate enhanced fibrosis. Similar results were discussed by Parra et al 39 Less marked pathological changes were found in group III.…”

The Role of Cell Proliferation and Extracellular Matrix Accumulation Induced by Food Additive Butylated Hydroxytoluene in Uterine Leiomyoma

“…BHT exposure also increased collagen I, III, and V expressions and altered both the telomerase and apoptosis-related expressions, along with further epithelial cell injury. Collectively, these studies indicate that BHT potentially affects fibrosis progression [ 57 ].…”

Fibrosis Is a Basement Membrane-Related Disease in the Cornea: Injury and Defective Regeneration of Basement Membranes May Underlie Fibrosis in Other Organs

“…In some ways, the monolayer of alveolar epithelial type I cells overlying the alveolar BM ( Figure 8 B) and underlying interstitial space in lung alveoli is similar in organization to that of the corneal endothelial cells, Descemet’s membrane, and corneal stroma. Many toxic agents associated with idiopathic pulmonary fibrosis (IPF) ( Figure 8 C,D) and other fibrotic lung pathologies, such as tobacco smoke, bleomycin, paraquat, and butylated hydroxytoluene, produce chronic injury to the alveolar epithelial type I and II cells, and likely injury to the underlying BM [ 57 , 58 ]. Although there has been limited direct study of the ultrastructure and composition of the alveolar BM in these conditions, ultrastructural abnormalities, breaks, and convolution of the alveolar BM were clearly noted in transmission electron microscopic studies of IPF and other fibrotic lung diseases [ 57 , 58 ].…”

“…Many toxic agents associated with idiopathic pulmonary fibrosis (IPF) ( Figure 8 C,D) and other fibrotic lung pathologies, such as tobacco smoke, bleomycin, paraquat, and butylated hydroxytoluene, produce chronic injury to the alveolar epithelial type I and II cells, and likely injury to the underlying BM [ 57 , 58 ]. Although there has been limited direct study of the ultrastructure and composition of the alveolar BM in these conditions, ultrastructural abnormalities, breaks, and convolution of the alveolar BM were clearly noted in transmission electron microscopic studies of IPF and other fibrotic lung diseases [ 57 , 58 ]. Fibrosis in interstitial lung diseases has been classically identified as fibrous tissue accumulation in the pulmonary interstitium within the alveolar walls bounded by the alveolar epithelial and capillary endothelial BMs [ 57 ].…”