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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.

journal_name

Mol Cell Biochem

journal_title

Molecular and cellular biochemistry

authors

Zhu L,Hao Y,Guan H,Cui C,Tian S,Yang D,Wang X,Zhang S,Wang L,Jiang H

doi

10.1007/s11010-012-1474-9

subject

Has Abstract

pub_date

2013-01-01 00:00:00

pages

53-62

issue

1-2

eissn

0300-8177

issn

1573-4919

journal_volume

373

pub_type

杂志文章

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