PDGFR-β modulates vascular smooth muscle cell phenotype via IRF-9/SIRT-1/NF-κB pathway in subarachnoid hemorrhage rats

Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism
Weifeng WanJiping Tang

Abstract

Platelet-derived growth factor receptor-β (PDGFR-β) has been reported to promote phenotypic transformation of vascular smooth muscle cells (VSMCs). The purpose of this study was to investigate the role of the PDGFR-β/IRF9/SIRT-1/NF-κB pathway in VSMC phenotypic transformation after subarachnoid hemorrhage (SAH). SAH was induced using the endovascular perforation model in Sprague-Dawley rats. PDGFR-β small interfering RNA (siRNA) and IRF9 siRNA were injected intracerebroventricularly 48 h before SAH. SIRT1 activator (resveratrol) and inhibitor (EX527) were administered intraperitoneally 1 h after SAH induction. Twenty-four hours after SAH, the VSMC contractile phenotype marker α-smooth muscle actin (α-SMA) decreased, whereas the VSMC synthetic phenotype marker embryonic smooth muscle myosin heavy chain (Smemb) increased. Both PDGFR-β siRNA and IRF9 siRNA attenuated the induction of nuclear factor-κB (NF-κB) and enhanced the expression of α-SMA. The SIRT1 activator (resveratrol) preserved VSMC contractile phenotype, significantly alleviated neurological dysfunction, and reduced brain edema. However, these beneficial effects of PDGFR-β siRNA, IRF9 siRNA and resveratrol were abolished by the SIRT1 inhibitor (EX527). This study show...Continue Reading

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Citations

Jul 7, 2020·Journal of Cellular and Molecular Medicine·Ying ZhangNaijin Zhang
Oct 5, 2019·CNS Neuroscience & Therapeutics·Badih J DaouAditya S Pandey
Feb 5, 2021·Journal of Lipid and Atherosclerosis·Yoojin JungSun Sik Bae
Jun 6, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Yanyan ZhangXiangchun Shen
Nov 11, 2021·Reviews in the Neurosciences·Yanhong SongPing Zhao
Nov 20, 2021·Frontiers in Cardiovascular Medicine·Baohui YuanLi-Long Pan

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Methods Mentioned

BETA
acetylation
protein assay
Fluorescence

Software Mentioned

GraphPad Prism
ImageJ
ARRIVE

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