Partial pneumonectomy of telomerase null XXXX carrying shortened telomeres initiates cell growth arrest resulting in a limited compensatory growth response.

@entity1 @entity10205 @entity19 @entity409 @entity3207 @entity21324 @entity358
Telomerase mutations and significantly shortened chromosomal @entity10205 have recently been implicated in @entity1 lung pathologies. Natural telomere @entity3207 is an inevitable consequence of aging, which is also a risk factor for development of @entity358 . However, the impact of shortened @entity409 on the ability of lung cells to respond to significant challenge is still largely unknown. We have previously shown that lungs of late generation, telomerase null B6.Cg- @entity21324 (tm1Rdp) @entity19 feature alveolar simplification and chronic stress signaling at baseline, a phenocopy of aged lung. To determine the role telomerase plays when the lung is challenged, B6.Cg- @entity21324 (tm1Rdp) @entity19 carrying shortened @entity10205 and wild-type controls were subjected to partial pneumonectomy. We found that telomerase activity was strongly induced in alveolar epithelial type 2 cells (AEC2) of the remaining lung immediately following surgery. Eighty-six percent of wild-type animals survived the procedure and exhibited a burst of early compensatory growth marked by upregulation of proliferation, stress response, and DNA repair pathways in AEC2. In B6.Cg- @entity21324 (tm1Rdp) @entity19 carrying shortened @entity10205 , response to pneumonectomy was characterized by decreased survival, diminished compensatory lung growth, attenuated distal lung progenitor cell response, persistent DNA damage, and cell growth arrest. Overall, survival correlated strongly with telomere length. We conclude that functional telomerase and properly maintained @entity10205 play key roles in both long-term survival and the early phase of compensatory lung growth following partial pneumonectomy.
