Gadolinium-promoted precipitation of calcium phosphate is associated with profibrotic activation of RAW 264.7 macrophages

Gadolinium-promoted precipitation of calcium phosphate is associated with profibrotic activation of RAW 264.7 macrophages
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钆促进的磷酸钙沉淀与 RAW 264.7 巨噬细胞的促纤维化激活有关

DOI:
10.1016/j.tiv.2010.05.004
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发表时间:
2010-09-01
影响因子:
3.2
通讯作者:
Wang, Kui
Wang, Kui
中科院分区:
医学3区
文献类型:
--
作者:
Gou, Bao-Di;Bian, Sha;Wang, Kui

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钆基造影剂现在与肾源性系统性纤维化(NSF)有关。钆类在NSF发病机制中起作用的确切机制尚不完全清楚。在这项研究中,我们评估了氯化钆(GdCl 3)对磷酸钙沉淀的影响,并研究了含钆沉淀物在巨噬细胞促纤维化激活中的作用。在一个自由漂移系统中,诱导时间显着减少与GdCl 3的浓度增加,伴随着改变的形态和组成的沉淀。在完全细胞培养基中,添加GdCl 3导致形成约200-300 nm的颗粒。在RAW 264.7巨噬细胞的体外细胞模型中,GdCl 3通过激活PKC和ERK信号通路增加TGF-β 1和IL-6的产生。我们的研究结果表明,氯化钆促进磷酸钙沉淀和诱导巨噬细胞的促纤维化激活。(C)2010爱思唯尔有限公司版权所有。
Gadolinium-based contrast agents are now being linked to nephrogenic systemic fibrosis (NSF). The exact mechanism by which gadolinium species act in the pathogenesis of NSF is not fully understood. In this study, we evaluated the effect of gadolinium chloride (GdCl3) on the precipitation of calcium phosphate, and examined the role of the gadolinium-containing precipitates in the profibrotic activation of macrophages. In a free-drift system, the induction time was markedly reduced with increasing concentration of GdCl3, accompanied by alterations of morphology and composition of the precipitates. In complete cell culture medium, the addition of GdCl3 resulted in formation of particles around 200-300 nm. In an in vitro cellular model with RAW 264.7 macrophages, GdCl3 increased the production of TGF-beta 1 and IL-6 via the activation of PKC and ERK signaling pathway. Our findings demonstrate that GdCl3 promotes calcium phosphate precipitation and induces profibrotic activation of macrophages. (C) 2010 Elsevier Ltd. All rights reserved.