IRF5 Mediates Artery Inflammation in Salt-Sensitive Hypertension by Regulating STAT1 and STAT2 Phosphorylation to Increase ESM1 Transcription: Insights from Bioinformatics and Mechanistic Analysis DOI Open Access
Qiaoyu Shao, Hao Wang, Shicheng Li

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(8), P. 3722 - 3722

Published: April 15, 2025

Salt-sensitive hypertension (SSH) is closely associated with arterial inflammation, yet its molecular mechanisms remain unclear. In this study, we utilized deoxycorticosterone acetate (DOCA)-salt-induced hypertensive mice, which exhibited elevated blood pressure and significant inflammation. Single-cell RNA sequencing (scRNA-seq) identified interferon regulatory factor 5 (IRF5) downstream targets, signal transducer activator of transcription (STAT), as key regulators these inflammatory changes. vivo, IRF5 levels were significantly in the DOCA group, while STAT1 STAT2 protein comparable to those normal salt group. However, nuclear phosphorylated (pSTAT1) (pSTAT2) markedly higher Furthermore, scRNA-seq analysis showed increased expression endothelial cells (ECs) both human mouse aorta samples. vitro, knockdown artery ECs led a reduction pSTAT1 pSTAT2 expression. These results suggest that promotes phosphorylation, enabling their translocation. Additionally, indicated positive correlation between cell-specific molecule 1 (ESM1) STAT1/STAT2. Using UCSC JASPAR databases, multiple binding sites for STAT1::STAT2 dimer on ESM1 promoter. Luciferase reporter assays revealed enhanced following pSTAT1::pSTAT2 binding, pinpoint potential sites. Chromatin Immunoprecipitation Quantitative PCR (ChIP-qPCR) further confirmed specific findings highlight critical role IRF5-pSTAT1::pSTAT2-ESM1 pathway pathogenesis SSH therapeutic targets.

Language: Английский

Editorial: Research and development of new treatments for hypertension DOI
Aleksandar Jovanović

European Journal of Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 177318 - 177318

Published: Jan. 1, 2025

Language: Английский

Citations

0
Editorial: Research and development of new treatments for hypertension DOI
Aleksandar Jovanović

European Journal of Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 177321 - 177321

Published: Feb. 1, 2025

Language: Английский

Citations

0
Identification, characterization, and molecular docking of immunomodulatory peptides in Astragalus (Astragalus membranaceus (Fisch.)Bge) seed protein hydrolysates DOI

Yu Zhao,

He Teng,

Zhongxian Yu

et al.

Food Chemistry, Journal Year: 2025, Volume and Issue: 480, P. 143631 - 143631

Published: March 8, 2025

Language: Английский

Citations

0
IRF5 Mediates Artery Inflammation in Salt-Sensitive Hypertension by Regulating STAT1 and STAT2 Phosphorylation to Increase ESM1 Transcription: Insights from Bioinformatics and Mechanistic Analysis DOI Open Access
Qiaoyu Shao, Hao Wang, Shicheng Li

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(8), P. 3722 - 3722

Published: April 15, 2025

Salt-sensitive hypertension (SSH) is closely associated with arterial inflammation, yet its molecular mechanisms remain unclear. In this study, we utilized deoxycorticosterone acetate (DOCA)-salt-induced hypertensive mice, which exhibited elevated blood pressure and significant inflammation. Single-cell RNA sequencing (scRNA-seq) identified interferon regulatory factor 5 (IRF5) downstream targets, signal transducer activator of transcription (STAT), as key regulators these inflammatory changes. vivo, IRF5 levels were significantly in the DOCA group, while STAT1 STAT2 protein comparable to those normal salt group. However, nuclear phosphorylated (pSTAT1) (pSTAT2) markedly higher Furthermore, scRNA-seq analysis showed increased expression endothelial cells (ECs) both human mouse aorta samples. vitro, knockdown artery ECs led a reduction pSTAT1 pSTAT2 expression. These results suggest that promotes phosphorylation, enabling their translocation. Additionally, indicated positive correlation between cell-specific molecule 1 (ESM1) STAT1/STAT2. Using UCSC JASPAR databases, multiple binding sites for STAT1::STAT2 dimer on ESM1 promoter. Luciferase reporter assays revealed enhanced following pSTAT1::pSTAT2 binding, pinpoint potential sites. Chromatin Immunoprecipitation Quantitative PCR (ChIP-qPCR) further confirmed specific findings highlight critical role IRF5-pSTAT1::pSTAT2-ESM1 pathway pathogenesis SSH therapeutic targets.

Language: Английский

Citations

0