Vascular Health and Risk Management (Oct 2023)
RGS5 as a Biomarker of Pericytes, Involvement in Vascular Remodeling and Pulmonary Arterial Hypertension
Abstract
Guofang Lu,1,2,* Rui Du,3,* Yali Liu,1 Shumiao Zhang,1 Juan Li,1 Jianming Pei1 1Department of Physiology and Pathophysiology, National Key Discipline of Cell Biology, Fourth Military Medical University, Xi’an, 710032, People’s Republic of China; 2State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, 710032, People’s Republic of China; 3Institute for Biomedical Sciences of Pain, Tangdu Hospital, Fourth Military Medical University, Xi’an, 710038, People’s Republic of China*These authors contributed equally to this workCorrespondence: Juan Li; Jianming Pei, Email [email protected]; [email protected]: 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.Methods: 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.Results: 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.Conclusion: 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.Keywords: pulmonary arterial hypertension, pericytes, RGS5, pulmonary microvasculature, vascular remodeling
