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Fibroblast Response to Gadolinium Role for Platelet-Derived Growth Factor Receptor

机译:血小板衍生的生长因子受体对成纤维细胞的d作用

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Objective: The purpose of this study was to assess the effects of gadolinium (Gd~3+), provided as gadolinium chloride, on fibroblast function. Materials and Methods: Human dermal fibroblasts in monolayer culture and intact skin in organ culture were exposed to the lanthanide metal (1-20 muM). Results: Increased proliferation was observed, in association with upregu-lation of matrix metalloproteinase-1 and tissue inhibitor of metalloprotein-ases-1, without an apparent increase in production of type I procollagen. A platelet-derived growth factor (PDGF) receptor-blocking antibody inhibited fibroblast proliferation in response to Gd~(3+) as did inhibitors of signaling pathways-that is, mitogen-activated protein kinase and phosphatidylinosi-tol-3 kinase pathways-that are activated by PDGF. Conclusion: The responses to gadolinium chloride are similar to responses previously seen with chelated Gd~(3+) in clinically used magnetic resonance imaging contrast agents. Fibroblast responses appear to reflect Gd~(3+)-induced PDGF receptor activation and downstream signaling. Increased dermal fibroblast proliferation in conjunction with effects on matrix metalloproteinase-1 and tissue inhibitor of metalloproteinases-1 could contribute to the fibroplastic/fibrotic changes seen in the lesional skin of individuals with nephrogenic systemic fibrosis.
机译:目的:本研究的目的是评估氯化g(Gd〜3 +)对成纤维细胞功能的影响。材料和方法:将单层培养的人真皮成纤维细胞和器官培养的完整皮肤暴露于镧系金属(1-20μM)。结果:观察到增殖增加,与基质金属蛋白酶-1和金属蛋白酶-1的组织抑制剂的上调相关,而I型原胶原的产生没有明显增加。血小板衍生生长因子(PDGF)受体阻断抗体可抑制Gd〜(3+)的成纤维细胞增殖,这是信号传导途径抑制剂(即促分裂原激活的蛋白激酶和磷脂酰肌醇-tol-3激酶途径)的抑制剂。由PDGF激活。结论:对氯化g的反应类似于先前在临床使用的磁共振成像造影剂中对螯合的Gd〜(3+)的反应。成纤维细胞反应似乎反映了Gd〜(3+)诱导的PDGF受体激活和下游信号传导。真皮成纤维细胞增殖的增加,以及对基质金属蛋白酶-1和金属蛋白酶-1组织抑制剂的影响,可能会导致肾原性系统性纤维化患者的病灶皮肤出现纤维化/纤维化变化。

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