Upregulated TSP1 and CD47 expression in the lung in nitrofen‐induced congenital diaphragmatic hernia

BACKGROUND: Persistent pulmonary hypertension remains a major cause of mortality and morbidity in congenital diaphragmatic hernia (CDH). The secreted glycoprotein thrombospondin-1 (TSP1), a ligand for receptor CD47, is widely expressed on both systemic and pulmonary vascular cells. TSP1-CD47 signaling has been reported to be one of the pathogeneses of pulmonary hypertension (PH). METHODS: After creating a nitrofen-induced CDH rat model, fetuses were sacrificed on D17, D19 and D21 and divided into a control group and a CDH group. Quantitative real-time polymerase chain reaction was performed to determine the pulmonary gene expression of TSP1, CD47 and Runx3 (a regulator of TSP1). An immunofluorescence study was performed to evaluate the expression and localization of TSP1, CD47 and Runx3. RESULTS: The relative mRNA expression of pulmonary TSP1, CD47 and Runx3 on D21 was significantly increased in the CDH group (p = 0.005, p = 0.001, p = 0.046, and p = 0.002, respectively). The immunofluorescence study also confirmed the overexpression of TSP1, CD47 and Runx3 in the CDH group. CONCLUSION: Our results provide evidence that TSP1-CD47 signaling is involved in the pathogenesis of PH in a nitrofen-induced CDH model. Our data suggest that anti-CD47 antibodies can be novel therapeutic targets for the treatment of PH in CDH.