LPS induces RGS-1 to promote infectious intracranial aneurysm formation and rupture by accelerating smooth muscle cell phenotypic switching.

Autor: Hu X; Department of Cardiology, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, China., He X; Department of Cardiology, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou, China., Zhang W; Department of Cardiology, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, China., Jin C; Department of Cardiology, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, China., Deng C; Department of Cardiology, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, China., Ma Y; Department of Cardiology, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, China., Chen P; Department of Cardiology, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, China., Ma S; Department of Cardiology, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, China., Zhao R; Department of Cardiology, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, China. Electronic address: kouke80@126.com., Shi B; Department of Cardiology, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, China. Electronic address: shibei2147@163.com.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2024 Dec 05; Vol. 142 (Pt B), pp. 113203. Date of Electronic Publication: 2024 Sep 22.
DOI: 10.1016/j.intimp.2024.113203
Abstrakt: Objective: Patients with infectious intracranial aneurysms (IIAs) have high mortality rates. Sepsis is an important condition that induces IIA. Smooth muscle cell (SMC) phenotypic switching may have a critical effect on sepsis-induced IIA, but its role remains unclear. Hence, we aimed to identify sepsis-induced target genes involved in SMC phenotypic switching and their underlying mechanisms.
Methods and Results: RNA sequencing and bioinformatics analyses of samples from patients with intracranial aneurysms and sepsis identified RGS-1 as a common differentially expressed gene (DEG) involved in SMC phenotypic switching. Experimental verification demonstrated that lipopolysaccharide (LPS), a critical molecule in sepsis, increased RGS-1 levels, promoted SMC phenotypic switching and proliferation, and upregulated the expression of matrix metalloproteinases and inflammatory factors. Furthermore, qRT-PCR and immunofluorescence experiments confirmed that RGS-1 knockdown under LPS stimulation inhibited SMC phenotypic switching, cell proliferation, and decreases in matrix metalloproteinases and inflammatory factors. Mechanistically, western blotting, bioinformatics analyses, and chip assays revealed that RGS-1 activates the JNK-P38 pathway to promote SMC phenotypic switching and is regulated by the transcription factor STAT1.
Conclusion: LPS induces RGS-1 to promote IIA formation and rupture by accelerating SMC phenotypic switching.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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