Fibroblast growth factor 21 plays an inhibitory role in vascular calcification in vitro through OPG/RANKL system

被引：25

作者：

Cao, Fangying ^{[1
]}

Liu, Xiaoxiao ^{[1
]}

Cao, Xiangrong ^{[2
]}

Wang, Shaoping ^{[1
]}

Fu, Kun ^{[3
]}

Zhao, Yejing ^{[1
]}

Shen, Fang ^{[4
]}

Liu, Jinghua ^{[1
]}

机构：

[1] Capital Med Univ, Beijing Inst Heart Lung & Blood Vessel Dis, Beijing Anzhen Hosp, Dept Cardiol, Beijing, Peoples R China

[2] Capital Med Univ, Beijing Anzhen Hosp, Beijing Inst Heart Lung & Blood Vessel Dis, Dept Cardiac Surg, Beijing, Peoples R China

[3] Beijing Aerosp Gen Hosp, Dept Cardiol, Beijing, Peoples R China

[4] Nanchang Univ, Grad Sch Med, Nanchang, Jiangxi, Peoples R China

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2017年 / 491卷 / 03期

关键词：

Vascular calcification; Fibroblast growth factor 21; Osteoblastic differentiation; Apoptosis; Signaling pathway; SMOOTH-MUSCLE-CELLS; MOUSE MODEL; BONE LOSS; PATHWAY; ATHEROSCLEROSIS; APOPTOSIS; RANKL; FGF21; MICE; OSTEOPOROSIS;

D O I：

10.1016/j.bbrc.2017.07.160

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Vascular calcification is prevalent and associated with adverse outcome without available therapy. The benefits of fibroblast growth factor (FGF)-21 on metabolism and atherosclerosis make it a promising therapeutic agent for vascular calcification. We investigated the effects of FGF21 on vascular smooth muscle cell (VSMC) calcification by culturing rat VSMCs in a calcifying medium for 9days. FGF21 markedly attenuated mineral deposition and apoptosis at the indicated time points. In the presence of FGF21, the expression levels of osteoblastic protein including bone morphogenic protein-2, alkaline phosphatase(ALP), runt-related transcription factor(RUNX)-2 and nuclear factor-kappa B ligand (RANKL) were down-regulated, whereas the expression of osteoprotegerin (OPG) increased. Knockdown of OPG significantly impaired inhibition of FGF21 on apoptosis and the expression of pro-apoptotic genes including caspase-3 and Box and osteoblastic - promoting markers including ALP, RUNX-2 and RANKL. Furthermore, FGF21 facilitated the phosphoryl of AKT but suppressed P38, while OPG knockdown attenuated the effects. LY29400 (inhibitor of PI3K) abrogated the activation of PI3K/AKT and SB203580 (inhibitor of P38) abolished the inhibition of FGF21 on P38, while alteration was observed in the expression of RUNX-2. FGF21 inhibited VSMCs calcification via OPG/RANKL system, and through P38 andPI3K/AKT pathways. (C) 2017 Published by Elsevier Inc.

引用

页码：578 / 586

页数：9

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