Research Paper Volume 16, Issue 10 pp 8980—8997
Higher expression of TSR2 aggravating hypertension via the PPAR signaling pathway
- 1 Department of Cardiology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
- 2 Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, National Clinical Research Center for Cardiovascular Diseases, Chaoyang 100029, Beijing, China
Received: August 30, 2023 Accepted: December 7, 2023 Published: May 29, 2024
https://doi.org/10.18632/aging.205852How to Cite
Copyright: © 2024 Meng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Hypertension is a complex disease with unknown causes. Therefore, it’s crucial to deeply study its molecular mechanism. The hypertension dataset was obtained from Gene Expression Omnibus data base (GEO), and miRNA regulating central hub genes was screened via weighted gene co-expression network (DEGs) and gene set enrichment (GSEA). Cell experiments validated TSR2’s role and the PPAR signaling pathway through western blotting. 500 DEGs were identified for hypertension, mainly enriched in actin cross-linking, insulin signaling, PPAR signaling, and protein localization. Eight hub genes (SEC61G, SRP14, Liy AR, NIP7, SDAD1, POLR1D, DYNLL2, TSR2) were identified. Four hub genes (LYAR, SDAD1, POLR1D, TSR2) exhibited high expression levels in the hypertensive tissue samples, while showing low expression levels in the normal tissue samples. This led us to speculate that they may have relevant regulatory effects on hypertension. When TSR2 was knocked down in the hypertension peripheral blood mononuclear cells (PBMC) model, the critical proteins in the PPAR signaling pathway (FABP, PPAR, PLTP, ME1, SCD1, CYP27, FABP1, OLR1, CPT-1, PGAR, CAP, ADIPO, MMP1, UCP1, ILK, PDK1 UBC AQP7) were downregulated. This also occurred in the hypertension peripheral blood mononuclear cells (PBMC) + TSR2_ OV model. TSR2 is highly expressed in individuals with hypertension and may play a significant role in the development of hypertension through the PPAR signaling pathway. TSR2 could serve as a molecular target for the early diagnosis and precise treatment of hypertension, providing a valuable direction for the mechanism research of this condition.
Abbreviations
GEO: Gene Expression Omnibus data base; DEGs: Screening of differently expressed genes; WGCNA: Weighted Gene Coexpression Network Analysis; GSEA: Gene set enrichment analysis; KD: knock down; OE: over expression; MAD: Median Absolute Deviation; TOM: topological overlap matrix; PPI: protein-protein interaction; GO: Gene Ontology Analysis; STRING: Search Tool for the Retrieval of Interacting Genes; KEGG: Kyoto Encyclopedia of Genes and Genomes analysis; CTD: Comparative Toxicogenomics Database; FC: fold change; FDR: false discovery rate; PBMC: peripheral blood mononuclear cells; SHR: spontaneously hypertensive rats; SHRSP: spontaneously hypertensive stroke-prone; ROS: Reactive Oxygen Species; PPARs: peroxisome proliferators-activated receptors; FAO: Fatty Acid Oxidation; CAT: Catalase; GPX: Glutathione peroxidase; SOD: Superoxide Dismutase.