Decreased ZONAB expression promotes excessive transdifferentiation of alveolar epithelial cells in hyperoxia-induced bronchopulmonary dysplasia
| Autor: | Xindong Xue, Yujiao Xing, Yongyan Shi, Ana Hou, Jianhua Fu, Lin Qiao, Jun Li |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine education Cell Down-Regulation Hyperoxia Lung injury 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Genetics medicine Animals Rats Wistar Cells Cultured Bronchopulmonary Dysplasia Epithelial cell differentiation Chemistry Transdifferentiation General Medicine Transfection respiratory system Cell biology DNA-Binding Proteins Disease Models Animal 030104 developmental biology medicine.anatomical_structure 030228 respiratory system Alveolar Epithelial Cells Cell Transdifferentiation Female medicine.symptom |
| Zdroj: | International Journal of Molecular Medicine. |
| ISSN: | 1791-244X 1107-3756 |
| DOI: | 10.3892/ijmm.2018.3413 |
| Popis: | Previous studies by our group have confirmed excessive transdifferentiation of alveolar epithelial cells (AECs) in a hyperoxia‑induced bronchopulmonary dysplasia (BPD) model, but the underlying mechanism have remained elusive. The transcription factor zonula occludens 1‑associated nucleic acid binding protein (ZONAB) has the biological functions of inhibition of epithelial cell differentiation and promotion of epithelial cell proliferation. The aim of the present study was to explore the regulatory effect of ZONAB on the transdifferentiation and proliferation of AECs in a model of hyperoxia‑induced lung injury. Newborn Wistar rats were randomly allocated to a model group (inhalation of 85% O2) or a control group (inhalation of normal air), and ZONAB expression in lung tissues was detected at different time‑points. Type II AECs (AEC II) isolated from normal newborn rats were primarily cultured under an atmosphere of 85 or 21% O2, and ZONAB expression in the cells was examined. The primary cells were further transfected with ZONAB plasmid or small interfering (si)RNA and then exposed to hyperoxia, and the indicators for transdifferentiation and proliferation were measured. The present study indicated that ZONAB expression in AEC II of the BPD rats was significantly decreased from 7 days of exposure to hyperoxia onwards. In the AEC II isolated from normal neonatal rats, ZONAB expression in the model group was also reduced compared with that in the control group. After transfection with the plasmid pCMV6‑ZONAB, the expression of aquaporin 5 (type I alveolar epithelial cell marker) decreased and the expression of surfactant protein C (AEC II marker), proliferating‑cell nuclear antigen and cyclin D1 increased, which was opposite to the effects of ZONAB siRNA. Transfection with pCMV6‑ZONAB also alleviated excessive transdifferentiation and inhibited proliferation of AEC II induced by hyperoxia treatment. These results suggest that ZONAB expression in AEC II decreases under hyperoxia conditions, which promotes transdifferentiation and inhibits proliferation of AECs. This may, at least in part, be the underlying mechanism of lung epithelial injury in the hyperoxia-induced BPD model. |
| Databáze: | OpenAIRE |
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