Blocking the ERK1/2 signal pathway can inhibit S100A12 induced human aortic smooth muscle cells damage.

Abstract

Increased levels of S100A12 and activated matrix metalloproteinase 2/9 (MMP-2/9) produced by human aortic smooth muscle cells (HASMCs) have recently implicated in the development of thoracic aortic disease. In the present study, we investigated the effect of S100A12 on HASMCs and identified the intracellular signal pathways involved by Western blot. The results were shown that up-expression of S100A12 in HASMCs induced cell apoptosis and inhibited cell proliferation. Additionally, S100A12 significantly increased the expression of MMP-2, MMP-9, and VCAM-1 in HASMCs at translational levels. Furthermore, our results also showed that S100A12 induced HASMCs damage by increased related proteins expression was mediated by the activation of ERK1/2 signal pathway, whereas p38 MAPK had no effect on those processes. Blocked the activation of ERK1/2 could decrease S100A12 induced the apoptosis and inhibited cell proliferation of HASMCs. In conclusion, these results indicated that S100A12 could increase the expression of MMP-2, MMP-9, and vascular cell adhesion molecule 1 (VCAM-1) in HASMCs via activation of ERK1/2 signal pathway, which leads to injury of HASMCs. Therefore, antagonists of ERK1/2 may be useful for treating thoracic aortic dissection.

• Authors: Wanli Jiang, Zhiwei Wang, Zhipeng Hu, Hongbing Wu, Rui Hu, Xiaoping Hu, Zongli Ren, Jizhen Huang
• Journal: Cell biology international (Cell Biol Int) Vol. 41 Issue 12 Pg. 1307-1315 (Dec 2017) ISSN: 1095-8355 [Electronic] England
• PMID: 28816402 (Publication Type: Journal Article)
• Copyright: © 2017 International Federation of Cell Biology.

Chemical References

• Flavonoids
• Imidazoles
• Protein Kinase Inhibitors
• Pyridines
• S100A12 Protein
• S100A12 protein, human
• Mitogen-Activated Protein Kinases
• MMP2 protein, human
• Matrix Metalloproteinase 2
• MMP9 protein, human
• Matrix Metalloproteinase 9
• SB 203580
• 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one

Topics

• Aorta (cytology, drug effects, enzymology, metabolism)
• Apoptosis (drug effects, physiology)
• Cell Proliferation (physiology)
• Cells, Cultured
• Flavonoids (pharmacology)
• Humans
• Imidazoles (pharmacology)
• MAP Kinase Signaling System (drug effects, physiology)
• Matrix Metalloproteinase 2 (metabolism)
• Matrix Metalloproteinase 9 (metabolism)
• Mitogen-Activated Protein Kinases (antagonists & inhibitors, metabolism)
• Muscle, Smooth, Vascular (metabolism)
• Myocytes, Smooth Muscle (drug effects, enzymology, metabolism)
• Protein Kinase Inhibitors (pharmacology)
• Pyridines (pharmacology)
• S100A12 Protein (antagonists & inhibitors, metabolism)