Altered expression of cyclins and cdks in premature infant baboon model of bronchopulmonary dysplasia
Altered expression of cyclins and cdks in premature infant baboon model of bronchopulmonary dysplasia
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DOI：
10.1089/152308604771978426
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发表时间：
2004-02-01
影响因子：
6.6
通讯作者：
Ravi, D
中科院分区：
文献类型：
--
作者：
Das, KC;Ravi, D
支气管肺发育不良（BPD）是早产儿的一种慢性肺部疾病，导致高发病率。 BPD 的病理生理学包括氧化损伤、气压/容积损伤和肺部修复障碍。由于肺部发育、分化和修复需要细胞分裂，我们假设早产儿氧气暴露中细胞周期失调可能导致 BPD 的演变。在这项研究中，我们研究了调节细胞周期 G1 和 G2 期转变的细胞周期蛋白和细胞周期蛋白依赖性激酶 (cdks) 的表达。我们在此报告，早产狒狒在呼吸窘迫时细胞周期蛋白 D1、细胞周期蛋白 E 和细胞周期蛋白 A 的表达受到调节。此外，这些早产动物中 cdk1 或 cdk4 的表达也受到调节。在暴露于 PRN 氧气 6 或 14 天的 125 日龄动物和 140 日龄动物中，视网膜母细胞瘤蛋白的磷酸化逐渐降低。这些结果表明，由于细胞周期蛋白和 cdk 表达的改变，受损上皮的修复可能以无序的方式进行，这是 BPD 的特征。因此，细胞周期调控的改变可能是 BPD 进化的一个重要因素。
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.