RGS5 as a Biomarker of Pericytes, Involvement in Vascular Remodeling and Pulmonary Arterial Hypertension.
RGS5 as a Biomarker of Pericytes, Involvement in Vascular Remodeling and Pulmonary Arterial Hypertension.
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DOI：
10.2147/vhrm.s429535
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发表时间：
2023
影响因子：
2.9
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中科院分区：
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肺动脉高压（PAH）是一种以平均肺动脉压持续升高为特征的危及生命的疾病。肺血管重构在PAH中起重要作用。确定一个关键的驱动基因来调节肺微血管的血管重塑对于PAH管理至关重要。使用Gene Expression Omnibus（GEO）GSE 117261、GSE 48149、GSE 113439、GSE 53408和GSE 16947数据集鉴定差异表达的基因。利用加权基因共表达网络分析构建共表达网络。采用加权基因共表达网络分析、GEO 2 R分析、支持向量机递归特征剔除和鲁棒秩聚合秩分析4种算法筛选PAH的新特征和关键特征。G蛋白信号传导调节因子5（RGS 5），一种促凋亡/抗增殖蛋白，调节血管平滑肌细胞中的动脉张力和血压。使用逆转录-定量PCR（RT-qPCR）测定PAH和正常小鼠中RGS 5的表达。用免疫荧光法检测RGS 5和周细胞的位置。GEO和RT-qPCR分析显示，与正常组相比，PAH组RGS 5表达上调。在单细胞RNA测序分析中，在周细胞中富集单细胞中的RGS 5表达。在PAH的肺微血管中检测到RGS 5与周细胞共定位。RGS 5通过周细胞调节肺微血管的血管重塑和PAH的发生，为PAH的发生和创新治疗提供了新的思路和策略。
Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by a sustained rise in mean pulmonary artery pressure. Pulmonary vascular remodeling serves an important role in PAH. Identifying a key driver gene to regulate vascular remodeling of the pulmonary microvasculature is critical for PAH management. Differentially expressed genes were identified using the Gene Expression Omnibus (GEO) GSE117261, GSE48149, GSE113439, GSE53408 and GSE16947 datasets. A co-expression network was constructed using weighted gene co-expression network analysis. Novel and key signatures of PAH were screened using four algorithms, including weighted gene co-expression network analysis, GEO2R analysis, support vector machines recursive feature elimination and robust rank aggregation rank analysis. Regulator of G-protein signaling 5 (RGS5), a pro-apoptotic/anti-proliferative protein, which regulate arterial tone and blood pressure in vascular smooth muscle cells. The expression of RGS5 was determined using reverse transcription-quantitative PCR (RT-qPCR) in PAH and normal mice. The location of RGS5 and pericytes was detected using immunofluorescence. Compared with that in the normal group, RGS5 expression was upregulated in the PAH group based on GEO and RT-qPCR analyses. RGS5 expression in single cells was enriched in pericytes in single-cell RNA sequencing analysis. RGS5 co-localization with pericytes was detected in the pulmonary microvasculature of PAH. RGS5 regulates vascular remodeling of the pulmonary microvasculature and the occurrence of PAH through pericytes, which has provided novel ideas and strategies regarding the occurrence and innovative treatment of PAH.