Li Xu1, Jun-Tian Liu2, Kai Li3, Sheng-Yu Wang4, Shouzhu Xu5. 1. Department of Pharmacology, Xi'an Jiaotong University School of Medicine, Xi'an 710061, People's Republic of China; Department of Pharmacy, The First Affiliated Hospital of Xi'an Medical University, Xi'an 710077, People's Republic of China; Hospital Management Institute of Xi'an Medical University, Xi'an 710077, People's Republic of China. 2. Department of Pharmacology, Xi'an Jiaotong University School of Medicine, Xi'an 710061, People's Republic of China. Electronic address: ljt@mail.xjtu.edu.cn. 3. Department of Cardiology, Xi'an Medical University, Xi'an 710021, People's Republic of China. 4. Department of Intensive Care Unit, The First Affiliated Hospital of Xi'an Medical University, Xi'an 710077, People's Republic of China. 5. Department of Pharmacology, Xi'an Jiaotong University School of Medicine, Xi'an 710061, People's Republic of China.
Abstract
AIMS: C-reactive protein (CRP) and matrix metalloproteinase (MMP)-9 are involved in the inflammation of atherosclerosis lesions. Genistein (Gen) has been demonstrated to exert beneficial effect on the cardiovascular system. However, it remains unclear whether Gen produces anti-inflammatory effect in vascular smooth muscle cells (VSMCs). Therefore, we investigated the effects of Gen on CRP and MMP-9 expressions induced by angiotensin (Ang) II in VSMCs and the related molecular mechanism. MAIN METHODS: Rat VSMCs were cultured, and Ang II was used as a stimulant for CRP and MMP-9 expressions. CRP level was measured by ELISA. The mRNA and protein expressions of related indexes were identified by reverse transcription-polymerase chain reaction and western blot, respectively. KEY FINDINGS: Gen inhibited Ang II-stimulated CRP and MMP-9 mRNA and protein expressions in concentration- and time-dependent manners. Additionally, Gen ameliorated Ang II-induced p-ERK1/2, p-p38 and NF-κB expressions, antagonized Ang II-downregulated peroxisome proliferation-activated receptor (PPAR) γ and estrogen receptor (ER) β expressions. After treating the VSMCs with GW9662 or ICI182780 in Gen treated groups, inhibitory effect of Gen on CRP and MMP-9 expressions were antagonized in Ang II-stimulated VSMCs. The treatment of VSMCs with ICI182780 abolished downregulations of p-p38/p-ERK1/2, and antagonized upregulation of PPARγ by Gen in Ang II-stimulated VSMCs. Moreover, the inhibitory effect of Gen on Ang II-stimulated NF-κB expression was abolished after preincubation of VSMCs with GW9662 in Gen treated groups. SIGNIFICANCE: Gen exerts anti-inflammatory property via the ER-p38/ERK1/2-PPARγ-NF-κB-CRP/MMP-9 signal pathway in Ang II-stimulated VSMCs.
AIMS: C-reactive protein (CRP) and matrix metalloproteinase (MMP)-9 are involved in the inflammation of atherosclerosis lesions. Genistein (Gen) has been demonstrated to exert beneficial effect on the cardiovascular system. However, it remains unclear whether Gen produces anti-inflammatory effect in vascular smooth muscle cells (VSMCs). Therefore, we investigated the effects of Gen on CRP and MMP-9 expressions induced by angiotensin (Ang) II in VSMCs and the related molecular mechanism. MAIN METHODS:Rat VSMCs were cultured, and Ang II was used as a stimulant for CRP and MMP-9 expressions. CRP level was measured by ELISA. The mRNA and protein expressions of related indexes were identified by reverse transcription-polymerase chain reaction and western blot, respectively. KEY FINDINGS:Gen inhibited Ang II-stimulated CRP and MMP-9 mRNA and protein expressions in concentration- and time-dependent manners. Additionally, Gen ameliorated Ang II-induced p-ERK1/2, p-p38 and NF-κB expressions, antagonized Ang II-downregulated peroxisome proliferation-activated receptor (PPAR) γ and estrogen receptor (ER) β expressions. After treating the VSMCs with GW9662 or ICI182780 in Gen treated groups, inhibitory effect of Gen on CRP and MMP-9 expressions were antagonized in Ang II-stimulated VSMCs. The treatment of VSMCs with ICI182780 abolished downregulations of p-p38/p-ERK1/2, and antagonized upregulation of PPARγ by Gen in Ang II-stimulated VSMCs. Moreover, the inhibitory effect of Gen on Ang II-stimulated NF-κB expression was abolished after preincubation of VSMCs with GW9662 in Gen treated groups. SIGNIFICANCE: Gen exerts anti-inflammatory property via the ER-p38/ERK1/2-PPARγ-NF-κB-CRP/MMP-9 signal pathway in Ang II-stimulated VSMCs.
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