Mice with Pulmonary Fibrosis Driven by Telomere Dysfunction.

Autor:	Povedano JM; Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre (CNIO), Melchor Fernández Almagro 3, Madrid 28029, Spain., Martinez P; Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre (CNIO), Melchor Fernández Almagro 3, Madrid 28029, Spain., Flores JM; Animal Surgery and Medicine Department, Faculty of Veterinary Science, Complutense University of Madrid, Madrid 28029, Spain., Mulero F; Molecular Imaging Unit, Spanish National Cancer Research Centre (CNIO), Melchor Fernández Almagro 3, Madrid 28029, Spain., Blasco MA; Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre (CNIO), Melchor Fernández Almagro 3, Madrid 28029, Spain. Electronic address: mblasco@cnio.es.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2015 Jul 14; Vol. 12 (2), pp. 286-99. Date of Electronic Publication: 2015 Jul 02.
DOI:	10.1016/j.celrep.2015.06.028
Abstrakt:	Idiopathic pulmonary fibrosis (IPF) is a degenerative disease of the lungs with an average survival post-diagnosis of 2-3 years. New therapeutic targets and treatments are necessary. Mutations in components of the telomere-maintenance enzyme telomerase or in proteins important for telomere protection are found in both familial and sporadic IPF cases. However, the lack of mouse models that faithfully recapitulate the human disease has hampered new advances. Here, we generate two independent mouse models that develop IPF owing to either critically short telomeres (telomerase-deficient mice) or severe telomere dysfunction in the absence of telomere shortening (mice with Trf1 deletion in type II alveolar cells). We show that both mouse models develop pulmonary fibrosis through induction of telomere damage, thus providing proof of principle of the causal role of DNA damage stemming from dysfunctional telomeres in IPF development and identifying telomeres as promising targets for new treatments. (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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