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

ABSTRACT: Lung diseases develop when telomeres are shortened beyond a critical point. We have constructed a mouse model in which the catalytic subunit of telomerase (mTert), or its catalytically inactive form (mTertCI), is expressed from the p21Cdkn1a promoter. We found that this particular expression of mTert reduces senescence of endothelial cells (EC) in lungs of aged mice, as well as emphysema and pulmonary perivascular fibrosis. We also show that mTert counteracts the decline in capillary density in aged mice and promotes the maintenance of high numbers of Cd34+ cells, identified as a subclass of endothelial cells with proliferative capacity. In line with these results, young p21+/Tert mice treated with a VEGF receptor inhibitor combined with hypoxia are also protected against senescence and emphysema induced by this treatment. The catalytic activity of mTert is required for all the effects observed. However, and unexpectedly, we found that both mTert and mTertCI expression significantly reduced p21 levels in the lungs of aged mice. mTert thus protects against age-related and induced loss of capillary vessels and subsequent lung emphysema.

ORGANISM(S): Mus musculus

PROVIDER: GSE165218 | GEO | 2023/06/29

REPOSITORIES: GEO

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