Mar 25, 2020

Cellular senescence limits acute lung injury induced by mechanical ventilation

BioRxiv : the Preprint Server for Biology
J. Blazquez-PrietoGuillermo M Albaiceta

Abstract

Different forms of lung injury can activate senescence pathways. Senescence has been involved in chronic lung diseases, but its role in the acute phase is less known. Acute lung injury activates a large variety of pathogenetic mechanisms that can lead to respiratory insufficiency. In some cases, mechanical ventilation may help to maintain gas exchange, but positive airway pressures can cause regional overdistension of alveolar units and further damage. Here, we report that acute lung injury and alveolar overstretching activate a lung senescent program aimed to limit apoptosis. A systematic pooling of transcriptomic data from animal models of lung injury demonstrates the enrichment of a specific senescence signature. In a clinically relevant, murine model of acid aspiration and mechanical ventilation, we observed the activation of the Tp53/Cdkn1a (p21) senescence pathway, increases in senescence-associated heterochromatin foci in alveolar cells and markers of DNA damage, chromatin reorganization and changes in the nuclear envelope. Autopsy samples from lungs of critically ill patients showed the increase in senescence-associated heterochromatin foci. Cell stretch per se was also able to activate the senescence response in an ex-...Continue Reading

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Mentioned in this Paper

Microarray Analysis
Size
Topical Dosage Form
Genome
Genes
Genomic Stability
Cell Differentiation Process
Normalize
Genomics
Tetraspanins

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