Role of the Wnt/β-catenin signaling pathway in regulating the phenotypic transformation of aortic valvular myofibroblasts to osteoblast-like cells
10.3760/cma.j.issn.0254-9026.2016.02.024
- VernacularTitle:Wnt/β-catenin信号通路对心脏瓣膜成肌纤维细胞向成骨细胞样表型转化的作用机制
- Author:
Yingnian SHEN
;
Hongjie WANG
;
Di CHEN
;
Gao XU
;
Yongsheng LI
- Publication Type:Journal Article
- Keywords:
Heart Valves;
Fibroblasts;
Wnt/-catenin;
Osteoblasts
- From:
Chinese Journal of Geriatrics
2016;35(2):209-213
- CountryChina
- Language:Chinese
-
Abstract:
Objective To elucidate the role of the Wnt/-catenin signaling pathway in regulating the phenotypic transformation of aortic valvular myofibroblasts to osteoblast-like cells.Methods Cultured primary valvular myofibroblastes isolated from porcine aortic valve leaflets were treated with oxidized low-density lipoprotein (ox-LDL) for different lengths of time:24 h,48 h and 72 h.The Wnt signaling pathway inhibitor Dickkopf-1 (DDK-1) was co-incubated with ox-LDL for 72 h.After cells harvest,the expression of myofibroblastic or osteoblast-like phenotype related markers,a-smooth muscle actin (α-SMA),bone morphogenetic protein 2 (BMP2),alkaline phosphatase (ALP) and corebinding factora-1 (Cbfα 1),was detected by Western blotting.The expression and sub cellular localization of β3-catenin was assessed by immunocytochemistry.Changes of the Wnt/β-catenin signaling pathway and the transformation of aortic valvular myofibroblast to osteoblast-like cells were monitored.Results BMP2,ALP and Cbfa 1 protein expression was not or barely detectable in the control group.However,after ox-LDL treatment,the expression of α SMA,BMP2,ALP and Cbfa 1 increased significantly (each P＜0.01) in a time-dependent manner (each P＜0.05).Besides,ox-LDL was also able to up-regulate the protein expression of β-catenin in a time-dependent manner (P＜0.05) and promoted its nuclear translocation.After DKK-1 treatment,the protein expression of β3 catenin and osteogenesis related markers was down regulated (P＜0.05).Conclusions The Wnt/β-catenin signaling pathway may play a crucial role in regulating the transformation of aortic valvular myofibroblasts to an osteoblast like phenotype.
