Wang Xueyan, Wan Huajing, Yang Shuo, Zhou Rong, Liao Yong, Wang Fan, Chen Ximin, Wu Zhiling
1 Department of Prenatal Diagnosis, Women and Children's Hospital of Sichuan Province, Chengdu, China.
2 Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, China.
J Int Med Res. 2018 Jul;46(7):2856-2865. doi: 10.1177/0300060518774998. Epub 2018 Jun 13.
Objective The study aimed to investigate the role of high Krüppel-like factor 5 (KLF5) expression on the pathogenesis of congenital cystic adenomatoid malformation of the lungs (CCAML) in mice. Methods A mouse model of high KLF5 expression in the lungs was established. KLF5 expression and the pulmonary lumen diameter were examined by immunohistochemistry to determine a successful model. Basement membrane damage and activity of matrix metalloproteinase-9 (MMP-9) were examined. After an adenovirus carrying KLF5 gene transfection in lung adenocarcinoma (H441) was created, changes in expression and activity of MMP-9 were determined. Results In a mouse model with high KLF5 expression, the pulmonary lumen was markedly enlarged, indicating establishment of CCAML. The basement membrane was degraded, and MMP-9 activity was significantly higher in the model group compared with the control group. Moreover, mice in a cellular model after transfection also showed higher MMP-9 activity than did controls. Conclusion High KLF5 expression may play a pivotal role in the pathogenesis of CCAML, partly through regulating the activity of MMP-9.
目的 本研究旨在探讨高表达的Krüppel样因子5(KLF5)在小鼠先天性肺囊性腺瘤样畸形(CCAML)发病机制中的作用。方法 建立肺组织中KLF5高表达的小鼠模型。通过免疫组化检测KLF5表达及肺腔直径,以确定模型构建成功。检测基底膜损伤及基质金属蛋白酶-9(MMP-9)活性。构建携带KLF5基因的腺病毒转染肺腺癌(H441)细胞后,测定MMP-9表达及活性变化。结果 在KLF5高表达的小鼠模型中,肺腔明显增大,表明成功构建了CCAML模型。模型组基底膜降解,MMP-9活性显著高于对照组。此外,转染后的细胞模型中的小鼠MMP-9活性也高于对照组。结论 KLF5高表达可能在CCAML发病机制中起关键作用,部分是通过调节MMP-9的活性实现的。