Effect of sinomenine on vascular smooth muscle cell dedifferentiation and neointima formation after vascular injury in mice.

Abstract

Sinomenine, a pure alkaloid extract from Sinomenium acutum, has anti-inflammatory and immunoregulatory functions. This study investigated the efficiency and the signalling pathways involved in the effect of sinomenine on vascular smooth muscle cell (VSMC) dedifferentiation in response to platelet-derived growth factor (PDGF)-BB stimulation and vascular injury. VSMCs were isolated from rat aorta and preincubated with sinomenine before being stimulated with PDGF-BB. WST and BrdU incorporation assays were used to evaluate VSMC proliferation. Flow cytometric analysis was performed for testing the cell cycle progression. The cell migration of VSMCs were analysed using a Transwell system. The expression of VSMC specific genes and signalling proteins were tested by Western blot. For the animal study, C57/BL6 mice were fed either normal rodent chow diets or sinomenine chow diets that supplemented with 0.09 % sinomenine (w/w) in the normal chows for 14 days before carotid artery wire injury. PDGF-BB activated the dedifferentiation of VSMCs characterised by decreased expression of SMA, Smoothelin and SM22α. However, sinomenine treatment preserved the dedifferentiation in response to PDGF-BB. The activations of mitogen-activated protein kinase extracellular signal-regulated kinases, Akt, GSK3β and STAT3 induced by PDGF-BB were also inhibited in sinomenine-treated VSMCs. In vivo evidence with wire-injured mice exhibited a reduction in neointimal area and an increase in smooth muscle-specific gene expression in the sinomenine-treated group. In this study, we found that sinomenine-suppressed VSMC phenotype switching induced by PDGF-BB in vitro and neointimal formation in vivo. Therefore, sinomenine is a potential candidate to be used in the treatment of vascular proliferative disease.

• Authors: Lihua Zhu, Yarong Hao, Hongjing Guan, Changping Cui, Song Tian, Da Yang, Xinan Wang, Shuming Zhang, Lang Wang, Hong Jiang
• Journal: Molecular and cellular biochemistry (Mol Cell Biochem) Vol. 373 Issue 1-2 Pg. 53-62 (Jan 2013) ISSN: 1573-4919 [Electronic] Netherlands
• PMID: 23065380 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Morphinans
• Muscle Proteins
• STAT3 Transcription Factor
• Stat3 protein, rat
• sinomenine
• Receptors, Platelet-Derived Growth Factor

Topics

• Animals
• Carotid Arteries (drug effects, pathology)
• Cell Cycle (drug effects)
• Cell Dedifferentiation (drug effects)
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Cells, Cultured
• Gene Expression (drug effects)
• MAP Kinase Signaling System
• Male
• Mice
• Mice, Inbred C57BL
• Morphinans (pharmacology)
• Muscle Proteins (genetics, metabolism)
• Muscle, Smooth, Vascular (cytology)
• Myocytes, Smooth Muscle (drug effects, physiology)
• Neointima (prevention & control)
• Phenotype
• Phosphorylation
• Protein Processing, Post-Translational (drug effects)
• Rats
• Rats, Sprague-Dawley
• Receptors, Platelet-Derived Growth Factor (metabolism)
• STAT3 Transcription Factor (metabolism)