Effects and mechanism of fibroblast growth factor 21 on rat vascular smooth muscle cells calcification
10.3760/cma.j.issn.0253-3758.2015.10.009
- VernacularTitle:成纤维细胞生长因子21对大鼠血管平滑肌钙化的影响及机制
- Author:
Kun FU
1
;
Yi XIN
;
Yuchen SHI
;
Xuwei ZHENG
;
Yuan LYU
;
Zhenye XU
;
Hua Jing LIU
Author Information
1. 100029,首都医科大学附属北京安贞医院心内科 北京市心肺血管疾病研究所
- Keywords:
Fibroblast growth factors;
Calcinosis;
PPAR gamma
- From:
Chinese Journal of Cardiology
2015;43(10):879-886
- CountryChina
- Language:Chinese
-
Abstract:
Objective To observe the effect and mechanism of fibroblast growth factor 21 (FGF21) on rat vascular smooth muscle cells (VSMCs) calcification in vitro.Methods VSMCs was treated with calcification medium containing calcium chloride and β-glycerophosphate to induce rat VSMCs calcification in vitro.VSMCs were divided into 5 groups: the control group (cultured in normal medium), the calcification group (incubated in calcified medium), the FGF21 group (cultured in calcified medium and FGF21), the PD166866 group (cultured in calcified medium and FGF21 and PD166866, inhibitor of fibroblast growth factor receptor-1 (FGFR1)), the GW9662 group (cultured in calcified medium and FGF21 and GW9662, inhibitor of peroxisome proliferators activated receptor-γ (PPAR-γ)).The calcification of VSMCs was detected by calcium content, alkaline phosphatase activity and alizarin red staining.The protein and mRNA expression of FGFR1, β-Klotho, osteocalcin and smooth muscle 22α (SM22α) were determined by western blot analysis and realtime-PCR, respectively.Results (1) The mRNA (P ＜ 0.01) and protein expressions of β-Klotho and FGFR1 were significantly downregulated in calcification group compared with control group (P ＜ 0.05 or 0.01).(2)The protein levels and mRNA expression of calcium content, alkaline phosphatase activity and osteocalcin were significantly downregulated, while the protein levels and mRNA of SM22α were significantly increased in FGF21 group compared with calcification group (all P ＜ 0.05).Moreover, alizarin red staining verified positive red nodules on calcified VSMCs was significantly reduced in FGF21 group than in calcification group.(3)Calcium content, alkaline phosphatase activity and alizarin red staining were similar between PD166866 group and calcification group (all P ＞ 0.05).(4) Calcium content, alkaline phosphatase activity and alizarin red staining were similar between GW9662 group and calcification group (all P ＞ 0.05).Conclusion The inhibition of VSMCs calcification by FGF21 is mediated by further downregulating FGFR1 and β-Klotho while activating PPAR-γpathways.
