2026-06-14T03:39:39Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/160612024-11-29T22:49:25Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Piñeiro-Hermida, Sergio
author
Martinez Rodriguez, Paula
author
Bosso, Giuseppe
author
Flores, Juana María
author
Saraswati, Sarita
author
Connor, Jane
author
Lemaire, Raphael
author
Blasco, MA
funder
AstraZeneca
funder
Botín Foundation
funder
Banco Santander
funder
Agencia Estatal de Investigación (España)
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Comunidad de Madrid (España)
funder
Unión Europea. Comisión Europea. European Research Council (ERC)
funder
Instituto de Salud Carlos III
2023-05-16T08:54:00Z
2023-05-16T08:54:00Z
2022-10-06
Nat Commun. 2022;13(1):5656.
10.1038/s41467-022-32771-6
2041-1723
Nature communications
36202783
http://hdl.handle.net/20.500.12105/16061
TRF1 is an essential component of the telomeric protective complex or shelterin. We previously showed that dysfunctional telomeres in alveolar type II (ATII) cells lead to interstitial lung fibrosis. Here, we study the lung pathologies upon telomere dysfunction in fibroblasts, club and basal cells. TRF1 deficiency in lung fibroblasts, club and basal cells induced telomeric damage, proliferative defects, cell cycle arrest and apoptosis. While Trf1 deletion in fibroblasts does not spontaneously lead to lung pathologies, upon bleomycin challenge exacerbates lung fibrosis. Unlike in females, Trf1 deletion in club and basal cells from male mice resulted in lung inflammation and airway remodeling. Here, we show that depletion of TRF1 in fibroblasts, Club and basal cells does not lead to interstitial lung fibrosis, underscoring ATII cells as the relevant cell type for the origin of interstitial fibrosis. Our findings contribute to a better understanding of proper telomere protection in lung tissue homeostasis.
eng
Consequences of telomere dysfunction in fibroblasts, club and basal cells for lung fibrosis development.
journal article
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