右心衰竭严重影响SLE相关性肺动脉高压（SLE-PAH）患者的预后，但其分子机制仍然未知。我们前期基于首创的SLE-PAH小鼠模型，利用转录组学测序发现SLE-PAH小鼠右心室纤维化通路明显激活，以及表达明显增加的PTN基因。进一步发现PTN能诱导心肌成纤维细胞的Wnt3a、β-catenin蛋白表达并促进β-catenin入核。本项目拟通过检测疾病相关患者和小鼠的血清PTN，评估PTN预测及诊断SLE-PAH导致的右心损伤的潜在价值。通过病毒构建心脏特异性沉默或过表达PTN的狼疮小鼠，探索PTN/Wnt/β-catenin在SLE-PAH导致的右心损伤过程中的作用，并利用狼疮小鼠心肌成纤维细胞研究该信号对胶原合成的影响。本项目的完成将阐明PTN/Wnt/β-catenin参与SLE-PAH导致的右心损伤的作用机制，为今后通过靶向针对该通路治疗SLE-PAH患者的右心损伤提供理论支持。

Right heart failure strongly worsens the prognosis of patients with SLE associated pulmonary arterial hypertension. However, the underlying molecular mechanism is still unknown. Based on the SLE-PAH mouse model we first created previously, we found that the fibrosis-related pathways were significantly activated and the expression of PTN gene was significantly increased in the right ventricular of SLE-PAH mice by using RNA sequencing technique. Furtherly we found that PTN increases Wnt3a and beta-catenin protein expression in cardiac fibroblasts and promotes beta-catenin protein to translocate into the nucleus. In this project, we will evaluate the potential value of PTN in predicting and diagnosing SLE-PAH caused right heart injury by detecting serum PTN level in patients and mice with related diseases. The role of PTN/Wnt/β-catenin in SLE-PAH caused right heart injury will be explored in cardiac PTN specific silenced or overexpressed lupus mice. Moreover, we will study the effect of PTN/Wnt/beta-catenin signal on collagen synthesis using cardiac fibroblasts from lupus mice. The completion of this project will clarify the mechanism of PTN/Wnt/beta-catenin in SLE-PAH caused right heart injury, and provide theoretical support for treating right heart injury in SLE-PAH patients by targeting PTN/Wnt/beta-catenin pathway in the future.