mTert induction in p21-positive cells counteracts capillary rarefaction and pulmonary emphysema.

Autor:	Lipskaia L; Institute for Lung Health, Justus Liebig University, Giessen, Germany.; INSERM U955 and Département de Physiologie, Hôpital Henri Mondor, FHU SENEC, AP-HP, 94010, Créteil, and Université Paris-Est Créteil (UPEC), Paris, France., Breau M; Marseille Cancer Research Centre (CRCM), U1068 INSERM, UMR7258 CNRS, UM105 Aix-Marseille University, Institut Paoli-Calmettes, Ligue Nationale Contre le Cancer (Equipe labellisée), Team Telomeres and Chromatin, Marseille, France., Cayrou C; Marseille Cancer Research Centre (CRCM), U1068 INSERM, UMR7258 CNRS, UM105 Aix-Marseille University, Institut Paoli-Calmettes, Ligue Nationale Contre le Cancer (Equipe labellisée), Team Telomeres and Chromatin, Marseille, France., Churikov D; Marseille Cancer Research Centre (CRCM), U1068 INSERM, UMR7258 CNRS, UM105 Aix-Marseille University, Institut Paoli-Calmettes, Ligue Nationale Contre le Cancer (Equipe labellisée), Team Telomeres and Chromatin, Marseille, France., Braud L; Marseille Cancer Research Centre (CRCM), U1068 INSERM, UMR7258 CNRS, UM105 Aix-Marseille University, Institut Paoli-Calmettes, Ligue Nationale Contre le Cancer (Equipe labellisée), Team Telomeres and Chromatin, Marseille, France., Jacquet J; Institute for Lung Health, Justus Liebig University, Giessen, Germany., Born E; Institute for Lung Health, Justus Liebig University, Giessen, Germany., Fouillade C; Institut Curie, Inserm U1021, CNRS UMR 3347, University Paris-Saclay, PSL Research University, Orsay, France., Curras-Alonso S; Institut Curie, PSL Research University, CNRS UMR3244, Sorbonne Université, Telomeres and Cancer, 75005, Paris, France., Bauwens S; Université Côte d'Azur, CNRS, Inserm, IRCAN, Faculty of Medicine, Nice, France., Jourquin F; Marseille Cancer Research Centre (CRCM), U1068 INSERM, UMR7258 CNRS, UM105 Aix-Marseille University, Institut Paoli-Calmettes, Ligue Nationale Contre le Cancer (Equipe labellisée), Team Telomeres and Chromatin, Marseille, France., Fiore F; Centre d'Immunophénomique, Aix Marseille Université, INSERM, CNRS UMR, Marseille, France., Castellano R; Marseille Cancer Research Centre (CRCM), TrGET Preclinical Platform, Institut Paoli-Calmettes, Inserm, CNRS, Aix Marseille Université, Marseille, France., Josselin E; Marseille Cancer Research Centre (CRCM), TrGET Preclinical Platform, Institut Paoli-Calmettes, Inserm, CNRS, Aix Marseille Université, Marseille, France., Sánchez-Ferrer C; Centro Nacional de Investigaciones Cardiovasculares Carlos III, 28029, Madrid, Spain., Giovinazzo G; Centro Nacional de Investigaciones Cardiovasculares Carlos III, 28029, Madrid, Spain., Lachaud C; Marseille Cancer Research Centre (CRCM), U1068 INSERM, UMR7258 CNRS, UM105 Aix-Marseille University, Institut Paoli-Calmettes, Team DNA Interstrand Crosslink Lesions and Blood Disorders, Marseille, France., Gilson E; Université Côte d'Azur, CNRS, Inserm, IRCAN, Faculty of Medicine, Nice, France., Flores I; Centro Nacional de Investigaciones Cardiovasculares Carlos III, 28029, Madrid, Spain.; Centro de Biologia Molecular Severo Ochoa, CSIC-UAM, Cantoblanco, Madrid, Spain., Londono-Vallejo A; Institut Curie, PSL Research University, CNRS UMR3244, Sorbonne Université, Telomeres and Cancer, 75005, Paris, France., Adnot S; Institute for Lung Health, Justus Liebig University, Giessen, Germany. Serge.Adnot@innere.med.uni-giessen.de.; INSERM U955 and Département de Physiologie, Hôpital Henri Mondor, FHU SENEC, AP-HP, 94010, Créteil, and Université Paris-Est Créteil (UPEC), Paris, France. Serge.Adnot@innere.med.uni-giessen.de., Géli V; Marseille Cancer Research Centre (CRCM), U1068 INSERM, UMR7258 CNRS, UM105 Aix-Marseille University, Institut Paoli-Calmettes, Ligue Nationale Contre le Cancer (Equipe labellisée), Team Telomeres and Chromatin, Marseille, France. vincent.geli@inserm.fr.
Jazyk:	angličtina
Zdroj:	EMBO reports [EMBO Rep] 2024 Mar; Vol. 25 (3), pp. 1650-1684. Date of Electronic Publication: 2024 Feb 29.
DOI:	10.1038/s44319-023-00041-1
Abstrakt:	Lung diseases develop when telomeres shorten beyond a critical point. We constructed a mouse model in which the catalytic subunit of telomerase (mTert), or its catalytically inactive form (mTert CI ), is expressed from the p21 Cdkn1a locus. Expression of either TERT or TERT CI reduces global p21 levels in the lungs of aged mice, highlighting TERT non-canonical function. However, only TERT reduces accumulation of very short telomeres, oxidative damage, endothelial cell (ECs) senescence and senile emphysema in aged mice. Single-cell analysis of the lung reveals that p21 (and hence TERT) is expressed mainly in the capillary ECs. We report that a fraction of capillary ECs marked by CD34 and endowed with proliferative capacity declines drastically with age, and this is counteracted by TERT but not TERT CI . Consistently, only TERT counteracts decline of capillary density. Natural aging effects are confirmed using the experimental model of emphysema induced by VEGFR2 inhibition and chronic hypoxia. We conclude that catalytically active TERT prevents exhaustion of the putative CD34 + EC progenitors with age, thus protecting against capillary vessel loss and pulmonary emphysema. (© 2024. The Author(s).)
Databáze:	MEDLINE
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