Role of P16,CyclinD1,and CDK4 in progressive reduction of alveolar epithelial cells during pulmonary fibrosis / 中国组织工程研究

ABSTRACT

BACKGROUND:Several studies have demonstrated that the number of alveolar epithelial cells decreases gradually as pulmonary fibrosis develops,but the reasons remain unknown.The expression of P16,CyclinD1,and CDK4 might be abnormal and P16-CyclinD1/CDK4 call cycle regulatory pathway may play an important role in the progressive reduction of alveolar epithelial cells during pulmonary fibrosis.OBJECTIVE:To investigate the dynamic expression of P16,CyclinD1,and CDK4 in the pulmonary tissue of bleomycin-inducad pulmonary fibrosis mice.METHODS:Pulmonary fibrosis was induced in 6-week-old KM mice by intratracheal injection of bleomycin(BLM group).The control mice were administered the same volume of physiological saline(control roup).At 3,7,14,and 28 days after modeling,hematoxylin-eosin staining was performed to observe the pathomorphological changes of lung tissue.P16,CydinD1,and CDK4protein expression in lung tissue was detected by immunohistochemistry and Western blot analysis.RESULTS AND CONCLUSION:In the BLM group,typical changes of pulmonary fibrosis were observed,and P16 and CDK4protein expression in the pulmonary tissue increased with time,but CyclinD1 protein expression was decreased with time.P16and CDK4 protein-positive calls in the BLM group were more than in the control group.Compared with the control group,P16protein expression in the BLM group was higher at 14 and 28 days after modeling(P<0.01)and CDK4 protein expression was higher at 7,14 and 28 days after modeling(P<0.05).CydinD1 protein-positive cells and protein expression were greater at 3and 7 days after modeling in the BLM group(P<0,05),but they were less at 28 days after modeling(P<0.05),than in the control group.At 14 days after modeling,CydinD1 protein-positive cells in the BLM group were more,but CyclinD1 protein expression was ess,than in the control group(P<0.05).These findings suggest that P16,CyclinD1 and CDK4 protein expression was abnormal during pulmonary fibrosis and P16-CyclinD1/CDK4 cell cycle regulatory pathway greatly results in progressive reduction of alveolar epithelial calls during this process.