84 prolonged ventilation causes p27kip1 induced cell cycle arrest in newborn rat lung

ABSTRACT Background: I_n vitro_ studies have demonstrated that mechanical stretch can inhibit lung cell proliferation. This inhibition of cell growth may lead to reduction of alveolar

formation and contribute to the development of bronchopulmonary dyplasia. Objective: To determine the effect of prolonged mechanical ventilation on cell-cycle regulation in a newborn rat

model. Methods: 7-day old Wistar rats were ventilated with low/moderate tidal volume and room air for 24 h. Following ventilation arterial blood gas analysis was performed and the animal was

killed. Lung tissues were processed for histological or molecular/protein analysis to determine (1) number of proliferating cells by BrdU and phospho-Histone H3 staining and (2) gene and

protein expression of cell cycle regulatory proteins by real-time PCR and Western blotting. Results: After 24 h of ventilation arterial blood gas values were within normal range but alveolar

formation was reduced. The number of proliferating cells was decreased (BrdU incorporation decreased from 10 to 3 % and phospho-histone H3 positive cells from 0.8 to 0.1%. Expression of

CyclinD1 and E1 mRNA and protein was markedly down-regulated. Instead, protein expression of the CDK inhibitor p27Kip1 was significantly increased while its phosphorylation at site T157,

T198 and T187 was decreased. Interestingly, CDK inhibitor p16Ink4a levels were decreased by ventilation. Conclusions: Prolonged mechanical ventilation causes cycle arrest of lung cells in

newborn rats by increased transcription and nuclear localization of the CDK inhibitor p27Kip1. These data may in part explain the arrest in alveolarization by mechanical ventilation of the

neonatal lung. ARTICLE PDF AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Pediatrics, Erasmus MC - Sophia Children's Hospital, Rotterdam, The Netherlands A A Kroon * Lung Biology

Research, Physiology and Experimental Medicine Program, Hospital for Sick Children, Toronto, ON, Canada A A Kroon, J Wang, Z Huang, M Kuliszewski & M Post Authors * A A Kroon View author

publications You can also search for this author inPubMed Google Scholar * J Wang View author publications You can also search for this author inPubMed Google Scholar * Z Huang View author

publications You can also search for this author inPubMed Google Scholar * M Kuliszewski View author publications You can also search for this author inPubMed Google Scholar * M Post View

author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Kroon, A., Wang, J.,

Huang, Z. _et al._ 84 Prolonged Ventilation Causes P27KIP1 Induced Cell Cycle Arrest in Newborn Rat Lung. _Pediatr Res_ 68 (Suppl 1), 45 (2010).

https://doi.org/10.1203/00006450-201011001-00084 Download citation * Issue Date: November 2010 * DOI: https://doi.org/10.1203/00006450-201011001-00084 SHARE THIS ARTICLE Anyone you share the

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