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Increased epithelial cell proliferation in very premature baboons with chronic lung disease
William M Maniscalco1, Richard H Watkins, Michael A O'Reilly
1Division of Neonatology, Strong Children's Research Center, Department of Pediatrics, University of Rochester, Rochester, New York 14642, USA. William_Maniscalco@URMC.Rochester.edu
Insights
Premature baboons exposed to oxygen and ventilation showed significantly increased lung cell proliferation, disrupting normal development. Chronic lung injury alters lung cell proliferation patterns, impacting lung growth and differentiation.
Area of Science:
- Pulmonary Medicine
- Developmental Biology
- Neonatology
Background:
- Normal lung development relies on coordinated cell proliferation.
- Chronic lung injury in premature infants can disrupt these normal proliferation patterns.
- Understanding these disruptions is crucial for managing bronchopulmonary dysplasia.
Purpose of the Study:
- To investigate the impact of chronic lung injury on lung cell proliferation patterns in premature baboons.
- To characterize changes in cell proliferation markers like Ki67 and pro-surfactant protein B (proSP-B) under injurious conditions.
Main Methods:
- Premature baboons (125 days gestation) were exposed to oxygen and ventilation for 6, 14, or 21 days.
- Lung tissue was analyzed for cell proliferation using the Ki67 marker.
- Expression of pro-surfactant protein B (proSP-B) was assessed in proliferating cells.
Main Results:
- Proliferating lung cells increased 2.5-8.5-fold in treated baboons compared to controls.
- By 14 days, proSP-B expressing cells increased ~2.5-fold, with 41% of proliferating cells expressing proSP-B.
- By 21 days, proliferation of proSP-B cells decreased, but non-proSP-B cells increased sevenfold.
Conclusions:
- Chronic lung injury in developing lungs causes significant alterations in normal cell proliferation patterns.
- These changes involve both pro-surfactant protein B-expressing and non-expressing cells.
- The findings highlight the complex cellular responses contributing to chronic lung disease development.
Abstract:
Coordinated proliferation of lung cells is required for normal lung growth and differentiation. Chronic injury to developing lung may disrupt normal patterns of cell proliferation. To examine patterns of cell proliferation in injured developing lungs, we investigated premature baboons delivered at 125 days gestation (approximately 67% of term) and treated with oxygen and ventilation for 6, 14, or 21 days (PRN). Each PRN treatment group contained 3 or 4 animals. During normal in utero lung development, the proportion of proliferating lung cells declined as measured by the cell-cycle marker Ki67. In the PRN group, the proportion of proliferating lung cells was 2.5-8.5-fold greater than in corresponding gestational controls. By 14 days of treatment, the proportion of cells that expressed pro-surfactant protein B (proSP-B) was ~2.5-fold greater than in gestational controls. In the PRN group, 41% of proliferating cells expressed proSP-B compared with 5.8% in the gestational controls. By 21 days of treatment, proliferation of proSP-B-expressing epithelial cells declined substantially, but the proportion of proliferating non-proSP-B-expressing cells increased approximately sevenfold. These data show that the development of chronic lung disease is associated with major alterations in normal patterns of lung-cell proliferation.