College of Veterinary Medicine, Northwest A&F University, Xianyang 712100, China.
Life Science Research Core Service, Northwest A&F University, Xianyang 712100, China.
Int J Mol Sci. 2023 Jun 1;24(11):9629. doi: 10.3390/ijms24119629.
Pulmonary arterial hypertension (PAH) is a rare but fatal disease characterized by elevated pulmonary vascular resistance and increased pressure in the distal pulmonary arteries. Systematic analysis of the proteins and pathways involved in the progression of PAH is crucial for understanding the underlying molecular mechanism. In this study, we performed tandem mass tags (TMT)-based relative quantitative proteomic profiling of lung tissues from rats treated with monocrotaline (MCT) for 1, 2, 3 and 4 weeks. A total of 6759 proteins were quantified, among which 2660 proteins exhibited significant changes (-value < 0.05, fold change < 0.83 or >1.2). Notably, these changes included several known PAH-related proteins, such as Retnla (resistin-like alpha) and arginase-1. Furthermore, the expression of potential PAH-related proteins, including Aurora kinase B and Cyclin-A2, was verified via Western blot analysis. In addition, we performed quantitative phosphoproteomic analysis on the lungs from MCT-induced PAH rats and identified 1412 upregulated phosphopeptides and 390 downregulated phosphopeptides. Pathway enrichment analysis revealed significant involvement of pathways such as complement and coagulation cascades and the signaling pathway of vascular smooth muscle contraction. Overall, this comprehensive analysis of proteins and phosphoproteins involved in the development and progression of PAH in lung tissues provides valuable insights for the development of potential diagnostic and treatment targets for PAH.
肺动脉高压（PAH）是一种罕见但致命的疾病，其特征是肺血管阻力升高和远端肺动脉压力增加。系统分析参与 PAH 进展的蛋白质和途径对于理解潜在的分子机制至关重要。在这项研究中，我们对用单环酸酯（MCT）处理 1、2、3 和 4 周的大鼠的肺组织进行了串联质量标签（TMT）相对定量蛋白质组学分析。共定量了 6759 种蛋白质，其中 2660 种蛋白质发生了显著变化（-值<0.05，倍数变化<0.83 或>1.2）。值得注意的是，这些变化包括几种已知的 PAH 相关蛋白，如 Retnla（抵抗素样α）和精氨酸酶-1。此外，通过 Western blot 分析验证了潜在的 PAH 相关蛋白，如 Aurora 激酶 B 和细胞周期蛋白 A2 的表达。此外，我们对 MCT 诱导的 PAH 大鼠的肺进行了定量磷酸蛋白质组学分析，鉴定出 1412 个上调的磷酸肽和 390 个下调的磷酸肽。途径富集分析显示，补体和凝血级联以及血管平滑肌收缩的信号通路等途径显著参与。总之，这项对肺组织中参与 PAH 发展和进展的蛋白质和磷酸蛋白质的全面分析为 PAH 的潜在诊断和治疗靶点的开发提供了有价值的见解。
