Abstract
Background: Bronchopulmonary dysplasia (BPD) is characterized by impaired alveolar and microvascular development. Claudin-18 is the only known lung-specific tight junction protein affecting the development and transdifferentiation of alveolar epithelium. Objective: We aimed to explore the changes in the expression of claudin-18, podoplanin, SFTPC, and the canonical WNT pathway, in a rat model of hyperoxia-induced BPD, and to verify the regulatory relationship between claudin-18 and the canonical WNT pathway by cell experiments. Methods: A neonatal rat and cell model of BPD was established by exposing to hyperoxia (85%). Hematoxylin and eosin (HE) staining was used to confirm the establishment of the BPD model. The mRNA levels were assessed using quantitative real-time polymerase chain reaction(qRT-PCR). Protein expression levels were determined using western blotting, immunohistochemical staining, and immunofluorescence. Results: As confirmed by HE staining, the neonatal rat model of BPD was successfully established. Compared to that in the control group, claudin-18 and claudin-4 expression decreased in the hyperoxia group. Expression of β-catenin in the WNT signaling pathway decreased, whereas that of p-GSK-3β increased. Expression of the AEC II marker SFTPC initially decreased and then increased, whereas that of the AEC I marker podoplanin increased on day 14 (P < 0.05). Similarly, claudin-18, claudin-4, SFTPC and β-catenin were decreased but podoplanin was increased when AEC line RLE-6TN exposed to 85% hyperoxia. And the expression of SFTPC was increased, the podoplanin was decreased, and the WNT pathway was upregulated when claudin-18 was overexpressed. Conclusions: Claudin-18 downregulation during hyperoxia might affect lung development and maturation, thereby resulting in hyperoxia-induced BPD. Additionally, claudin-18 is associated with the canonical WNT pathway and AECs transdifferentiation.