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Retracted: Pulmonary alveolar stem cells undergo senescence, apoptosis and differentiation by p53‐dependent and ‐independent mechanisms in telomerase deficient mice
Author(s) -
Zhang Kexiong,
Wang Lihui,
Chen Hao,
Shi Yao,
Liu Yingying,
Liu Jun,
Hong Xiaojing,
Liu JunPing
Publication year - 2021
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.13472
Subject(s) - telomerase , senescence , biology , telomere , telomerase reverse transcriptase , pulmonary fibrosis , stem cell , apoptosis , cellular differentiation , microbiology and biotechnology , cancer research , immunology , pathology , fibrosis , gene , genetics , medicine
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.