Abstract
Telomeres are distal chromosome regions associated with specific protein complexes that protect the chromosome against degradation and aberrations. Telomere maintenance capacity is an essential indication of healthy cell populations, and telomere damage is observed in processes such as malignant transformation, apoptosis, or cell senescence. At a cellular level, telomere damage may result from genotoxic stress, decreased activity of telomerase enzyme complex, dysfunction of shelterin proteins, or changes in expression of telomere-associated RNA such as TERRA. Clinical evidence suggests that mutation of telomerase genes (Tert/Terc) are associated with increased risk of congenital as well as age-related diseases (e.g., pneumonitis, idiopathic pulmonary fibrosis (IPF), dyskeratosis congenita, emphysema, nonspecific interstitial pneumonia, etc.). Thus, telomere length and maintenance can serve as an important prognostic factor as well as a potential target for new strategies of treatment for interstitial lung diseases (ILDs) and associated pulmonary pathologies.
Highlights
Telomeres are nucleoprotein complexes that assemble at the end of chromosomes
Povedano et al showed that the protein component of telomerase (Tert)−/− mice with shelterin Trf1 deletion, in alveolar epithelial type 2 cells, develop pulmonary fibrosis due to severe telomere protein cap dysfunction [38]. These findings indicate that telomere damage in alveolar epithelial type 2 cells is sufficient to cause spontaneous lung fibrosis in the elderly, and may be a major molecular defect causing Idiopathic pulmonary fibrosis (IPF) in humans [37]
Genetic mutations related to telomere maintenance are one of many genetic defects found in patients with familial IPF
Summary
Telomeres are nucleoprotein complexes that assemble at the end of chromosomes. They comprise tandem repeats of a short DNA sequence, such as TTAGGG for humans and other vertebrates [1]. Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease of unknown etiology and is the most common form of ILD. Various factors may be involved in the pathogenesis of ILD, such as chromosomal damage [7], DNA repair deficiencies [8] and epithelial-mesenchymal transition due to endoplasmic reticulum stress [9,10]. These factors may result in distinctive gene expression changes [11], which may serve as diagnostic markers [12], and in DNA damage under interstitial lung disease, under pulmonary fibrosis. In early treatment [14,15]
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