Research Paper Volume 15, Issue 11 pp 4625—4641
Short telomeres in alveolar type II cells associate with lung fibrosis in post COVID-19 patients with cancer
- 1 Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre (CNIO), Madrid E-28029, Spain
- 2 Servicio de Anatomía Patológica, Hospital Universitario Marqués de Valdecilla, Santander 39008, Spain
- 3 Servicio de Cirugía Torácica, Hospital Universitario Marqués de Valdecilla, Santander 39008, Spain
- 4 Servicio de Neumología Hospital Universitario Marqués de Valdecilla, Santander E-39008, Spain
- 5 Institute of Biomedicine and Biotechnology of Cantabria (IBBTEC), Cantabria, Santander E-39011, Spain
- 6 Instituto de Investigación Marqués de Valdecilla (IDIVAL), Santander E-39011, Spain
- 7 Departamento de Fisiología y Farmacología, Universidad de Cantabria, Santander E-39011, Spain
Received: March 30, 2023 Accepted: May 10, 2023 Published: June 7, 2023
https://doi.org/10.18632/aging.204755How to Cite
Copyright: © 2023 Martínez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease 2019 (COVID-19) pandemic. The severity of COVID-19 increases with each decade of life, a phenomenon that suggest that organismal aging contributes to the fatality of the disease. In this regard, we and others have previously shown that COVID-19 severity correlates with shorter telomeres, a molecular determinant of aging, in patient’s leukocytes. Lung injury is a predominant feature of acute SARS-CoV-2 infection that can further progress to lung fibrosis in post-COVID-19 patients. Short or dysfunctional telomeres in Alveolar type II (ATII) cells are sufficient to induce pulmonary fibrosis in mouse and humans. Here, we analyze telomere length and the histopathology of lung biopsies from a cohort of alive post-COVID-19 patients and a cohort of age-matched controls with lung cancer. We found loss of ATII cellularity and shorter telomeres in ATII cells concomitant with a marked increase in fibrotic lung parenchyma remodeling in post- COVID-19 patients compared to controls. These findings reveal a link between presence of short telomeres in ATII cells and long-term lung fibrosis sequel in Post-COVID-19 patients.
Abbreviations
ATI: alveolar type I cells; ATII: alveolar type II cells; IPF: Idiopathic pulmonary fibrosis; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; COVID-19: coronavirus disease 2019; ACE2: angiotensin-converting enzyme 2; Q-FISH: Quantitative telomere Fluorescence In Situ Hybridization; SMA: a-smooth muscle actin; pro-SPC: prosurfactant protein C.