Consequences of telomere dysfunction in fibroblasts, club and basal cells for lung fibrosis development

Sergio Piñeiro-Hermida, Paula Martínez, Giuseppe Bosso, Juana María Flores, Sarita Saraswati, Jane Connor, Raphael Lemaire and Maria A. Blasco ()
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Sergio Piñeiro-Hermida: Spanish National Cancer Centre (CNIO), Melchor Fernández Almagro 3
Paula Martínez: Spanish National Cancer Centre (CNIO), Melchor Fernández Almagro 3
Giuseppe Bosso: Spanish National Cancer Centre (CNIO), Melchor Fernández Almagro 3
Juana María Flores: Complutense University of Madrid
Sarita Saraswati: Spanish National Cancer Centre (CNIO), Melchor Fernández Almagro 3
Jane Connor: BioPharmaceuticals R&D, AstraZeneca
Raphael Lemaire: BioPharmaceuticals R&D, AstraZeneca
Maria A. Blasco: Spanish National Cancer Centre (CNIO), Melchor Fernández Almagro 3

Nature Communications, 2022, vol. 13, issue 1, 1-18

Abstract: Abstract 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.

Date: 2022
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DOI: 10.1038/s41467-022-32771-6

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