Pollack Daniel, Xiao Yuxuan, Shrivasatava Vibha, Levy Avi, Andrusier Miriam, D'Armiento Jeanine, Holz Marina K, Vigodner Margarita
Department of Biology, Stern College, Yeshiva University, New York, NY, USA.
Division of Pulmonary, Allergy & Critical Care Medicine, Department of Medicine, Columbia University, New York, NY, USA.
Toxicol Lett. 2015 Apr 16;234(2):120-30. doi: 10.1016/j.toxlet.2015.02.006. Epub 2015 Feb 10.
In this study, DNA arrays have been employed to monitor gene expression patterns in testis of mice exposed to tobacco smoke for 24 weeks and compared to control animals. The results of the analysis revealed significant changes in expression of several genes that may have a role in spermatogenesis. Cdk14 was chosen for further characterization because of a suggested role in the testis and in regulation of Wnt signaling. RT-PCR analysis confirmed down regulation of Cdk14 in mice exposed to cigarette smoke (CS). Cdk14 is expressed in all testicular cells; spermatogonia- and Sertoli-derived cell lines treated with cigarette smoke extract (CSE) in vitro showed down-regulation of CDK14 mRNA and protein levels as well as down-regulation of β-catenin levels. CS-induced down-regulation of CDK14 mRNA and protein levels was also observed in several lung epithelium-derived cell lines including primary normal human bronchial epithelial cells (NHBE), suggesting that the effect is not restricted to the testis. Similar to testicular cells, CS-induced down-regulation of CDK14 in lung cells correlated with decreased levels of β-catenin, a finding suggesting impaired Wnt signaling. In the lungs, CDK14 was localized to the alveolar and bronchial epithelium.
在本研究中,DNA阵列已被用于监测暴露于烟草烟雾24周的小鼠睾丸中的基因表达模式,并与对照动物进行比较。分析结果显示,几个可能在精子发生中起作用的基因的表达有显著变化。由于Cdk14在睾丸及Wnt信号调节中被认为有作用,因此被选择进行进一步表征。逆转录聚合酶链反应(RT-PCR)分析证实,暴露于香烟烟雾(CS)的小鼠中Cdk14表达下调。Cdk14在所有睾丸细胞中均有表达;体外经香烟烟雾提取物(CSE)处理的精原细胞和支持细胞系显示CDK14 mRNA和蛋白水平下调,以及β-连环蛋白水平下调。在包括原代正常人支气管上皮细胞(NHBE)在内的几种肺上皮细胞系中也观察到CS诱导的CDK14 mRNA和蛋白水平下调,这表明该效应不限于睾丸。与睾丸细胞类似,CS诱导的肺细胞中CDK14下调与β-连环蛋白水平降低相关,这一发现表明Wnt信号受损。在肺中,CDK14定位于肺泡和支气管上皮。