Airway Epithelial Telomere Dysfunction Drives Remodeling Similar to Chronic Lung Allograft Dysfunction.
DNA damage
airway fibrosis
club cells
senescence
telomere
Journal
American journal of respiratory cell and molecular biology
ISSN: 1535-4989
Titre abrégé: Am J Respir Cell Mol Biol
Pays: United States
ID NLM: 8917225
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
pubmed:
20
6
2020
medline:
24
11
2020
entrez:
20
6
2020
Statut:
ppublish
Résumé
Telomere dysfunction is associated with multiple fibrotic lung processes, including chronic lung allograft dysfunction (CLAD)-the major limitation to long-term survival following lung transplantation. Although shorter donor telomere lengths are associated with an increased risk of CLAD, it is unknown whether short telomeres are a cause or consequence of CLAD pathology. Our objective was to test whether telomere dysfunction contributes to the pathologic changes observed in CLAD. Histopathologic and molecular analysis of human CLAD lungs demonstrated shortened telomeres in lung epithelial cells quantified by teloFISH, increased numbers of surfactant protein C immunoreactive type II alveolar epithelial cells, and increased expression of senescence markers (β-galactosidase, p16, p53, and p21) in lung epithelial cells.
Identifiants
pubmed: 32551854
doi: 10.1165/rcmb.2019-0374OC
pmc: PMC7528921
doi:
Substances chimiques
Biomarkers
0
Uteroglobin
9060-09-7
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
490-501Subventions
Organisme : CSRD VA
ID : I01 CX002011
Pays : United States
Organisme : CSRD VA
ID : IK2 CX001034
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL139897
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL151552
Pays : United States
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