Effect of Notch1/Hes1 signal regulating the expression of CCAAT/enhancer-binding protein alpha on the proliferation and differentiation of type II alveolar epithelial cells induced by hyperoxia

doi:10.3969/j.issn.2095-4344.0386

Abstract

Abstract:

BACKGROUND: Notch1/Hes1 signal and CCAAT/enhancer-binding protein alpha (C/EBPα) play important roles in lung development and injury. Preliminary studies have shown that hyperoxia can induce abnormal proliferation and differentiation of type II alveolar epithelial cells (AECII), which is related to C/EBPα expression. But, whether Notch1/Hes1 signal is involved remains unclear.
OBJECTIVE: To investigate the effect of Notch1/Hes1 signal regulating C/EBPα on the proliferation and differentiation of AECII induced by hyperoxia.
METHODS: Human AECIIs were cultured in vitro, and randomly divided into air group, air activator group (Notch pathway activator Jagged1 protein, 500 μg/L), hyperoxia group (95% O2 and 5% CO2 mixture gas administered at the speed of 3 L/minute for 10 minutes), hyperoxia activator group (500 μg/L Notch pathway activator Jagged1 protein added at 30 minutes before oxygen administration). AECIIs of each group were collected after 24 hours of intervention. The expression of Notch1, Hes1 and C/EBPα at mRNA and protein levels was determined by RT-PCR and western blot assay. The proliferation of AECII was measured by cell counting kit-8 assay. Flow cytometry labeled AQP5 was applied to detect the differentiation of AECII.
RESULTS AND CONCLUSION: Compared with the air group, the mRNA and protein expression levels of Notch1, Hes1 and C/EBPα were increased significantly in the air activator group (P < 0.05), the proliferation of AECII was increased and the differentiation was reduced significantly (P < 0.05). In the hyperoxia and hyperoxia activator groups, the mRNA and protein expression levels of Notch1, Hes1 and C/EBPα were significantly decreased, the proliferation of AECII was decreased and the differentiation was increased significantly (P < 0.05). Compared with the hyperoxia group, the mRNA and protein expression levels of Notch1, Hes1 and C/EBPα were significantly increased in the hyperoxia activator group (P < 0.05), and the proliferation of AECII was increased and the differentiation was decreased significantly (P < 0.05). These results suggest that Notch1/Hes1 signal regulates the expression of C/EBPα and affects the proliferation and differentiation of AECII after exposure to hyperoxia.

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

Key words: Pulmonary Alveoli, Epithelial Cells, Hyperoxia, CCAAT-Enhancer-Binding Protein-alpha, Cell Proliferation, Cell Differentiation, Tissue Engineering

CLC Number:

R318

Wan Feng-yun, Lu Hong-yan, Wan Xue-qing, Hao Xiao-bo, Zhu Yue. Effect of Notch1/Hes1 signal regulating the expression of CCAAT/enhancer-binding protein alpha on the proliferation and differentiation of type II alveolar epithelial cells induced by hyperoxia[J]. Chinese Journal of Tissue Engineering Research, 2018, 22(32): 5209-5214.

Figures/Tables 2

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