Responses of human skin in organ culture and human skin fibroblasts to a gadolinium-based MRI contrast agent: comparison of skin from patients with end-stage renal disease and skin from healthy subjects.
Responses of human skin in organ culture and human skin fibroblasts to a gadolinium-based MRI contrast agent: comparison of skin from patients with end-stage renal disease and skin from healthy subjects.
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DOI：
10.1097/rli.0b013e3181e9436b
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发表时间：
2010-11
影响因子：
6.7
通讯作者：
Varani J
中科院分区：
文献类型：
--
作者：
DaSilva M;O'Brien Deming M;Fligiel SE;Dame MK;Johnson KJ;Swartz RD;Varani J
肾源性系统性纤维化（NSF）是一种发生于少数终末期肾病（ESRD）患者的临床综合征。在磁共振成像期间暴露于某些钆基造影剂（GBCA）似乎是一种触发因素。这种疾病的发病机制在很大程度上是未知的。本研究探讨了潜在的病理生理机制。在这里，我们比较了器官培养的皮肤和皮肤成纤维细胞的反应，从个人与终末期肾病的反应，健康对照受试者的Omniscan治疗。用Omniscan治疗ESRD患者的皮肤刺激基质金属蛋白酶-1（MMP-1）和金属蛋白酶组织抑制剂-1（TIMP-1）的产生，但不刺激I型前胶原的产生。同样的处理也刺激了透明质酸的产生。在正常对照皮肤中观察到类似的结果，但ESRD患者的基础水平较高。单层培养中的成纤维细胞产生相同的反应，但基于细胞是否从健康受试者或患有ESRD的受试者的皮肤中分离没有差异。这些数据表明，Omniscan暴露改变了负责调节皮肤中胶原蛋白周转的酶/抑制剂系统，并直接刺激透明质酸的产生。ESRD患者皮肤中I型前胶原、MMP-1、TIMP-1和透明质酸的基础水平较高，可能导致该患者人群对纤维化变化的敏感性，而纤维化变化可能由暴露于某些GBCA诱导。
Nephrogenic systemic fibrosis (NSF) is a clinical syndrome occurring in a small subset of patients with end stage renal disease (ESRD). Exposure to certain of the gadolinium-based contrast agents (GBCAs) during magnetic resonance imaging appears to be a trigger. The pathogenesis of the disease is largely unknown. The present study addresses potential patho-physiological mechanisms. Here we have compared responses in organ-cultured skin and skin fibroblasts from individuals with ESRD to responses of healthy control subjects to Omniscan treatment. Treatment of skin from ESRD patients with Omniscan stimulated production of matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinases-1 (TIMP-1), but not type I procollagen. The same treatment also stimulated an increase in hyaluronan production. Similar results were seen with skin from normal controls but basal levels were higher in ESRD patients. Fibroblasts in monolayer culture gave the same responses but there were no differences based on whether the cells were isolated from the skin of healthy subjects or those with ESRD. These data indicate that Omniscan exposure alters an enzyme / inhibitor system responsible for regulating collagen turnover in the skin and directly stimulates hyaluronan production. The higher basal levels of type I procollagen, MMP-1, TIMP-1 and hyaluronan in the skin from ESRD patients could contribute to the sensitivity of this patient population to fibrotic changes which might be induced by exposure to some of the GBCAs.