Exp Mol Med.  2015 Jun;47(6):e170. 10.1038/emm.2015.36.

Emodin prevents intima thickness via Wnt4/Dvl-1/beta-catenin signaling pathway mediated by miR-126 in balloon-injured carotid artery rats

• Hua JY
• He YZ
• Xu Y
• Jiang XH
• Ye W
• Pan ZM

• KMID: 2155424
• DOI: http://doi.org/10.1038/emm.2015.36

Abstract

Neointimal proliferation after vascular injury is a key mechanism of restenosis, a major cause of percutaneous transluminal angioplasty failure and artery bypass occlusion. Emodin, an anthraquinone with multiple physiological activities, has been reported to inhibit proliferation of vascular smooth muscle cells (VSMCs) that might cause intimal arterial thickening. Thus, in this study, we established a rat model of balloon-injured carotid artery and investigated the therapeutic effect of emodin and its underlying mechanism. Intimal thickness was analyzed by hematoxylin and eosin staining. Expression of Wnt4, dvl-1, beta-catenin and collagen was determined by immunohistochemistry and/or western blotting. The proliferation of VSMC was evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and electron microscopy. MicroRNA levels were quantified by real-time quantitative PCR. Emodin relieved injury-induced artery intimal thickness. Results of western blots and immunohistochemistry showed that emodin suppressed expression of signaling molecules Wnt4/Dvl-1/beta-catenin as well as collagen protein in the injured artery. In addition, emodin enhanced expression of an artery injury-related microRNA, miR-126. In vitro, MTT assay showed that emodin suppressed angiotensin II (AngII)-induced proliferation of VSMCs. Emodin reversed AngII-induced activation of Wnt4/Dvl-1/beta-catenin signaling by increasing expression of miR-126 that was strongly supported by transfection of mimic or inhibitor for miR-126. Emodin prevents intimal thickening via Wnt4/Dvl-1/beta-catenin signaling pathway mediated by miR-126 in balloon-injured carotid artery of rats.

MeSH Terms

Adaptor Proteins, Signal Transducing/*metabolism
Animals
Carotid Arteries/drug effects/metabolism/pathology
Carotid Artery Injuries/*drug therapy/metabolism/pathology
Cell Proliferation/drug effects
Emodin/*therapeutic use
Male
MicroRNAs/*metabolism
Phosphoproteins/*metabolism
Rats
Rats, Sprague-Dawley
Signal Transduction/drug effects
Tunica Intima/*drug effects/metabolism/pathology
Wnt4 Protein/*metabolism
beta Catenin/*metabolism
Adaptor Proteins, Signal Transducing
Emodin
MicroRNAs
Phosphoproteins
Wnt4 Protein
beta Catenin