利用公开的核糖核酸测序数据,我们将SCUBE1鉴定为一个BMPR2相关基因,该基因在来自携带致病性BMPR2突变的肺动脉高压(PAH)患者和无突变的对照患者的诱导多能干细胞-内皮细胞之间差异表达.内皮SCUBE1表达被已知的PAH触发因素降低,及其下调在体外概括了已知的BMPR2相关内皮病理表型。同时,从PAH啮齿动物模型和PAH患者获得的血浆中SCUBE1浓度降低,而血浆浓度与疾病严重程度的血液动力学标志物密切相关。一起来看,这些数据暗示SCUBE1是PAH发病机制的新贡献者,具有潜在的治疗作用,诊断,和预后应用。
Utilizing publicly available ribonucleic acid sequencing data, we identified SCUBE1 as a BMPR2-related gene differentially expressed between induced pluripotent stem cell-endothelial cells derived from pulmonary arterial hypertension (PAH) patients carrying pathogenic BMPR2 mutations and control patients without mutations. Endothelial SCUBE1 expression was decreased by known triggers of PAH, and its down-regulation recapitulated known BMPR2-associated endothelial pathophenotypes in vitro. Meanwhile, SCUBE1 concentrations were reduced in plasma obtained from PAH rodent models and patients with PAH, whereas plasma concentrations were tightly correlated with hemodynamic markers of disease severity. Taken together, these data implicate SCUBE1 as a novel contributor to PAH pathogenesis with potential therapeutic, diagnostic, and prognostic applications.