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. 2021 May;48(5):651-659.
doi: 10.1111/1440-1681.13472. Epub 2021 Feb 25.

Pulmonary alveolar stem cells undergo senescence, apoptosis and differentiation by p53-dependent and -independent mechanisms in telomerase deficient mice

Kexiong Zhang  1 , Lihui Wang  1 , Hao Chen  1 , Yao Shi  1 , Yingying Liu  1 , Jun Liu  1 , Xiaojing Hong  1 , Jun-Ping Liu  1   2   3
Affiliations

Pulmonary alveolar stem cells undergo senescence, apoptosis and differentiation by p53-dependent and -independent mechanisms in telomerase deficient mice

Kexiong Zhang et al. Clin Exp Pharmacol Physiol. 2021 May.

Abstract

Pulmonary senescence and fibrosis occur with deoxyribonucleic acid (DNA) damage response in the lungs deficient of telomerase. The molecular mechanism mediating pulmonary alveolar cell fates remains to be investigated. The present study shows that pulmonary alveolar epithelial type 2 cells (AEC2) (alveolar stem cells) undergo not only replicative senescence, but also apoptosis and differentiation in association with increased innate immune natural killer (NK) cells in telomerase knockout (KO) mice. Telomerase ribonucleic acid (RNA) component (TERC) deficiency results in increased senescence-associated heterochromatin foci marker HP1γ, p21, p16 and apoptosis-associated cleaved caspase-3 in AEC2. However, p53 deficiency in the Trp53-/- allele of the late generation of TERC KO mice attenuates the increased senescent and apoptotic markers significantly. Moreover, p53 deficiency has no significant effect on the increased gene expression of T1α (a marker of terminal differentiated alveolar epithelial type 1 cells [AEC1]) in AEC2 of the late generation of TERC KO mice. Collectively, our findings suggest that pulmonary senescence takes place in deficiency of telomerase RNA component with the alveolar stem cells undergoing p53-dependent senescence and apoptosis as well as p53-independent differentiation.

Keywords: apoptosis; differentiation; lung alveolar type 2 cells; p53; senescence; telomerase RNA component; telomere shortening.

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