Telomere dysfunction in alveolar epithelial cells causes lung remodeling and fibrosis.

ABSTRACT: Telomeres are short in type II alveolar epithelial cells (AECs) of patients with idiopathic pulmonary fibrosis (IPF). Whether dysfunctional telomeres contribute directly to development of lung fibrosis remains unknown. The objective of this study was to investigate whether telomere dysfunction in type II AECs, mediated by deletion of the telomere shelterin protein TRF1, leads to pulmonary fibrosis in mice (SPC-Cre TRF1^fl/fl mice). Deletion of TRF1 in type II AECs for 2 weeks increased γH2AX DNA damage foci, but not histopathologic changes in the lung. Deletion of TRF1 in type II AECs for up to 9 months resulted in short telomeres and lung remodeling characterized by increased numbers of type II AECs, α-smooth muscle actin⁺ mesenchymal cells, collagen deposition

SUBMITTER: Naikawadi RP 

PROVIDER: S-EPMC5033906 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature