title: Abnormal expression of telomerase/apoptosis limits type II alveolar epithelial cell replication in the early remodeling of usual interstitial pneumonia/idiopathic pulmonary fibrosis.
abstract: Idiopathic pulmonary fibrosis is a distinctive, usually fatal, type of chronic fibrosing interstitial pneumonia of unknown cause that increases in prevalence with advanced age, characterized by failure of alveolar re-epithelization and progressive scar formation. Recently, limitation of the replicative capacity of tissues determined by telomerase/apoptosis balance has been implicated in pathogenesis of age-related diseases. In this study, we validated the importance of the expression of type 2 alveolar epithelial cells telomerase protein and studied the relationships between telomerase and apoptosis in early remodeling of usual interstitial pneumonia. We determined type 2 alveolar epithelial cells density, telomerase expression, and apoptosis in surgical lung biopsies from 24 patients with usual interstitial pneumonia, and in normal lung tissues from 18 subjects. We used immunohistochemistry, deoxynucleotidyl transferase method of end labeling, electron microscopy, and histomorphometry to evaluate the amount of type 2 alveolar epithelial cells staining for surfactant-A, telomerase, and in situ detection of apoptotic cells. Unaffected areas of usual interstitial pneumonia and normal lung tissue had similar densities of type 2 alveolar epithelial cells, but a significant minor subpopulation of type 2 alveolar epithelial cells was telomerase positive and a large population was telomerase negative. A significant inverse association was found between low type 2 alveolar epithelial cell telomerase expression and high apoptosis in unaffected areas of usual interstitial pneumonia. Although type 2 alveolar epithelial cell telomerase expression was higher than apoptosis in NLT group, no significant association was found between them. Electron microscopy confirmed epithelial apoptosis, alveolar collapse, and initial fibroplasia. We conclude that abnormal type 2 alveolar epithelial cells telomerase/apoptosis balance may reduce alveolar epithelial regenerative capacity, thus contributing to the early remodeling response in usual interstitial pneumonia.
authors: Departament of Pathology, Faculdade de Medicina da Universidade de São Paulo, Brasil.
authors: Daniel Reis
authors: DR
authors: Waisberg
authors: João Valente
authors: JV
authors: Barbas-Filho
authors: Edwin Roger
authors: ER
authors: Parra
authors: Sandra
authors: S
authors: Fernezlian
authors: Carlos Roberto Ribeiro
authors: CR
authors: de Carvalho
authors: Ronaldo Adib
authors: RA
authors: Kairalla
authors: Vera Luiza
authors: VL
authors: Capelozzi
mesh_terms: D000368:Aged; D056809:Alveolar Epithelial Cells / Q000378:metabolism / Q000473:pathology*; D017209:Apoptosis / Q000502:physiology*; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000378:metabolism / Q000473:pathology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D011379:Prognosis; D020545:Respiratory Mucosa / Q000378:metabolism / Q000473:pathology; D019098:Telomerase / Q000378:metabolism*
chemical_list: D019098:Telomerase