[Expression and roles of CDK4 and p21 in lung tissues of premature rats with hyperoxia-induced chronic lung disease].
OBJECTIVE
The pathogenic mechanisms of chronic lung disease (CLD) of premature infants are not fully understood. Its final pathological changes have been shown to relate with lung cell proliferation. The aim of the study was to explore the relationship of the expression of cyclin dependent kinase 4 (CDK4) mRNA and cyclin dependent kinase inhibitor (CDKI) p21 mRNA with lung cell proliferation.


METHODS
Eighty premature rats were randomly assigned to a hyperoxia group and a control group (n=40 each). The hyperoxia group was exposed to high concentration of oxygen (FiO2 >0.90 and developed CLD. The control group was exposed to room air (FiO2 =0.21). The rats were randomly subdivided into groups sacrificed at 1, 3, 7, 14 and 21 days of exposure. Lung tissues were collected and made into 5 microm sections. Expression of proliferating cell nuclear antigen (PCNA) in lung tissues was detected by immunohistochemistry. Dynamic expression of CDK4 mRNA and p21 mRNA were detected by in situ hybridization. Lung histomorphology and fibrosis were observed by microscopy.


RESULTS
Expression of PCNA and CDK4 mRNA of lung cells in the hyperoxia group increased significantly after 7 days of exposure, and further increased after 14 and 21 days compared with controls. p21 mRNA expression in the hyperoxia group significantly increased after 1 and 3 days of exposure. After 7 days, p21 mRNA expression progressively decreased, but remained at a higher level than control through 21 days of exposure. PCNA expression was positively correlated to CDK4 mRNA expression (r=0.83, P < 0.05) and negatively correlated to p21 mRNA expression (r=-0.81, P < 0.05) in the hyperoxia group between 7 and 21 days of exposure.


CONCLUSIONS
Hyperoxia can induce lung cell proliferation in premature rats. The over-expression of CDK4 gene and the decreased expression of p21 gene in lung tissues may be associated with lung cell proliferation induced by hyperoxia.
Gao
Ying
Y
Department of Pediatrics, Second Affiliated Hospital, China Medical University, Shenyang, China. e_gaoying@163.com
Xue
Xin-Dong
XD
Li
Jin-Yang
JY
Wang
Ni
N
D000818:Animals; D000831:Animals, Newborn; D001997:Bronchopulmonary Dysplasia / Q000378:metabolism* / Q000473:pathology; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics*; D005260:Female; D006801:Humans; D018496:Hyperoxia / Q000150:complications*; D007231:Infant, Newborn; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008297:Male; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D011658:Pulmonary Fibrosis / Q000209:etiology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
D050759:Cyclin-Dependent Kinase Inhibitor p21; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; C495903:Cdk4 protein, rat; D051358:Cyclin-Dependent Kinase 4