Altered expression of cyclins and cdks in premature infant baboon model of bronchopulmonary dysplasia.
Bronchopulmonary dysplasia (BPD) is a chronic lung disease of premature infants, which results in substantial morbidity. The pathophysiology of BPD includes oxidant injury, baro/volutrauma, and disordered lung repair. As lung development, differentiation, and repair require cell division, we hypothesized dysregulation of the cell cycle in oxygen exposure of premature infants that may contribute to the evolution of BPD. In this investigation, we studied the expression of cyclins and cyclin-dependent kinases (cdks) that regulate transition from G1 and G2 phases of the cell cycle. We report here that expression of cyclin D1, cyclin E, and cyclin A is modulated in premature baboons in respiratory distress. In addition, the expression of cdk1 or cdk4 was also modulated in these premature animals. The phosphorylation of retinoblastoma protein was progressively decreased in 125-day animals and in 140-day animals exposed to 6 or 14 days of PRN oxygen. These results indicate that due to altered cyclin and cdk expression, the repair of injured epithelium may proceed in a disordered manner that is characteristic of BPD. Thus, altered cell cycle regulation may be an important factor in the evolution of BPD.
Das
Kumuda C
KC
Department of Molecular Biology, University of Texas Health Center at Tyler, Tyler, TX 75708, USA. kumuda.das@uthct.edu
Ravi
Dashnamoorthy
D
D000818:Animals; D000831:Animals, Newborn; D016203:CDC2 Protein Kinase / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D016213:Cyclins / Q000378:metabolism*; D004195:Disease Models, Animal; D005865:Gestational Age; D007150:Immunohistochemistry; D008168:Lung / Q000378:metabolism* / Q000473:pathology*; D008171:Lung Diseases / Q000378:metabolism* / Q000473:pathology*; D010215:Papio; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins; D016160:Retinoblastoma Protein / Q000378:metabolism
D016213:Cyclins; D011518:Proto-Oncogene Proteins; D016160:Retinoblastoma Protein; D016203:CDC2 Protein Kinase; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases