Upregulated TSP1 and CD47 expression in the lung in nitrofen-induced congenital diaphragmatic hernia
Upregulated TSP1 and CD47 expression in the lung in nitrofen-induced congenital diaphragmatic hernia
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DOI：
10.1111/ped.15447
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发表时间：
2023-01-01
影响因子：
1.4
通讯作者：
Takayasu，Hajime
中科院分区：
文献类型：
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作者：
Takayasu，Hajime
研究背景持续性肺动脉高压是先天性腹股沟疝（CDH）的主要发病和死亡原因。分泌的糖蛋白血小板反应蛋白-1（TSP 1）是受体CD 47的配体，广泛表达于全身和肺血管细胞。TSP 1-CD 47信号通路是肺动脉高压（PH）的发病机制之一。方法建立大鼠CDH模型，分别于D17、D19、D21处死胎鼠，分为对照组和CDH组。采用真实的实时定量聚合酶链反应测定肺组织中TSP 1、CD 47和Runx 3（TSP 1的调节因子）的基因表达。结果CDH组肺组织中TSP 1、CD 47和Runx 3的相对mRNA表达在D21时显著增加（p= 0.005，p = 0.001，p = 0.046和p = 0.002）;免疫荧光研究也证实了TSP 1，CD 47和Runx 3在CDH组中的过度表达。结论我们的结果提供了证据，TSP 1-CD 47信号转导参与了在除草醚诱导的CDH模型中PH的发病机制。我们的数据表明，抗CD 47抗体可以成为治疗CDH中PH的新治疗靶点。
BackgroundPersistent 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).MethodsAfter 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 ofTSP1,CD47andRunx3(a regulator ofTSP1). An immunofluorescence study was performed to evaluate the expression and localization of TSP1, CD47 and Runx3.ResultsThe relative mRNA expression of pulmonaryTSP1,CD47andRunx3on D21 was significantly increased in the CDH group (p= 0.005,p= 0.001,p= 0.046, andp= 0.002, respectively). The immunofluorescence study also confirmed the overexpression ofTSP1,CD47andRunx3in the CDH group.ConclusionOur 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.