通过生物信息学研究 H2-Ab1 在肺动脉高压血管重构中的作用。
Investigation into the role of H2-Ab1 in vascular remodeling in pulmonary arterial hypertension via Bioinformatics.
机构信息
Department of Respiratory Medicine, Affiliated Hospital of Shaoxing University, No. 999 South Zhongxing Road, Shaoxing, Zhejiang, 312000, China.
Center for General Practice Medicine, General Practice and Health Management Center, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, No. 158 Shangtang Road, Hangzhou, Zhejiang, 310014, China.
出版信息
BMC Pulm Med. 2024 Jul 15;24(1):342. doi: 10.1186/s12890-024-03156-w.
BACKGROUND
Pulmonary arterial hypertension (PAH) is a progressive disease of vascular remodeling characterized by persistent pulmonary arterial pressure elevation, which can lead to right heart failure and premature death. Given the complex pathogenesis and poor prognosis of PAH, the identification and investigation of biomarkers become increasingly critical for advancing further understanding of the disease.
METHODS
PAH-related datasets, GSE49114, GSE180169 and GSE154959, were downloaded from the publicly available GEO database. By performing WGCNA on the GSE49114 dataset, a total of 906 PAH-related key module genes were screened out. By carrying out differential analysis on the GSE180169 dataset, a total of 576 differentially expressed genes were identified. Additionally, the GSE154959 single-cell sequencing dataset was also subjected to differential analysis, leading to the identification of 34 DEGs within endothelial cells. By taking intersection of the above three groups of DEGs, five PAH-related hub genes were screened out, namely Plvap, Cyp4b1, Foxf1, H2-Ab1, and H2-Eb1, among which H2-Ab1 was selected for subsequent experiments.
RESULTS
A SuHx mouse model was prepared using the SU5416/hypoxia method, and the successful construction of the model was evaluated through Hematoxylin-Eosin staining, hemodynamic detection, fulton index, and Western Blot (WB). The results of WB and qRT-PCR demonstrated a significant upregulation of H2-Ab1 expression in SuHx mice. Consistent with the results of bioinformatics analysis, a time-dependent increase was observed in H2-Ab1 expression in hypoxia-treated mouse pulmonary artery endothelial cells (PAECs). To investigate whether H2-Ab1 affects the development and progression of PAH, we knocked down H2-Ab1 expression in PAECs, and found that its knockdown inhibited the viability, adhesion, migration, and angiogenesis, while concurrently promoted the apoptosis of PAECs.
CONCLUSION
H2-Ab1 could regulate the proliferation, apoptosis, adhesion, migration, and angiogenesis of PAECs.
背景
肺动脉高压（PAH）是一种以持续性肺动脉压升高为特征的血管重构性疾病，可导致右心衰竭和过早死亡。鉴于 PAH 的复杂发病机制和不良预后，生物标志物的鉴定和研究对于深入了解该疾病变得越来越重要。
方法
从公开的 GEO 数据库中下载了与 PAH 相关的数据集 GSE49114、GSE180169 和 GSE154959。通过对 GSE49114 数据集进行 WGCNA 分析，筛选出 906 个与 PAH 相关的关键模块基因。通过对 GSE180169 数据集进行差异分析，共鉴定出 576 个差异表达基因。此外，还对 GSE154959 单细胞测序数据集进行了差异分析，在血管内皮细胞中鉴定出 34 个 DEGs。通过对以上三组 DEGs 取交集，筛选出 5 个与 PAH 相关的枢纽基因，即 Plvap、Cyp4b1、Foxf1、H2-Ab1 和 H2-Eb1，其中选择 H2-Ab1 进行后续实验。
结果
采用 SU5416/缺氧法制备 SuHx 小鼠模型，通过苏木精-伊红（Hematoxylin-Eosin，HE）染色、血流动力学检测、 Fulton 指数和 Western blot（WB）评估模型构建的成功。WB 和 qRT-PCR 结果显示 SuHx 小鼠中 H2-Ab1 的表达显著上调。与生物信息学分析结果一致，缺氧处理的小鼠肺动脉内皮细胞（pulmonary artery endothelial cells，PAECs）中 H2-Ab1 的表达呈时间依赖性增加。为了研究 H2-Ab1 是否影响 PAH 的发生和发展，我们在 PAECs 中敲低 H2-Ab1 的表达，发现其敲低抑制了 PAECs 的活力、黏附、迁移和血管生成，同时促进了 PAECs 的凋亡。
结论
H2-Ab1 可以调节 PAECs 的增殖、凋亡、黏附、迁移和血管生成。
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