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首页> 外文期刊>Investigative radiology >Effects of magnetic resonance imaging contrast agents on human umbilical vein endothelial cells and evaluation of magnetic resonance imaging contrast media-triggered transforming growth factor-beta induction in dermal fibroblasts (HSF) as a model for nephrogenic systemic fibrosis.
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Effects of magnetic resonance imaging contrast agents on human umbilical vein endothelial cells and evaluation of magnetic resonance imaging contrast media-triggered transforming growth factor-beta induction in dermal fibroblasts (HSF) as a model for nephrogenic systemic fibrosis.

机译：磁共振成像造影剂对人脐静脉内皮细胞的影响以及磁共振成像造影剂触发的真皮成纤维细胞（HSF）中转化生长因子β诱导的评估，作为肾源性系统性纤维化的模型。

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RATIONALE AND OBJECTIVES: The objective of this study was to evaluate effects of 6 commercially available magnetic resonance contrast media (CM) on human umbilical vein endothelial cells (HUVEC) and the induction of transforming growth factor-beta (TGF-beta) in dermal fibroblasts (HSF) as a possible model for the pathogenesis of nephrogenic systemic fibrosis. METHODS: HUVECs were incubated with 10x and 20x of the molar standard blood concentration achieved with CM applications for magnetic resonance imaging examinations (10x and 20x concentration) for 24 hours using gadolinium-based CM Gadovist, Magnevist, Multihance, and Omniscan, as well as Teslascan (Manganese-based), and Resovist (Iron-based). Proliferation kinetics (PK), colony formation, and viability assays were performed. Additionally, human dermal fibroblasts (HSF) were incubated for 24 hours with 1x and 20x concentration in all 6 CM, and TGF-beta levels were assessed directly after the incubation period as well as on days 3 and 8 postincubation. RESULTS: HUVEC PK data show similar gains in cell numbers for all 6 CM in both concentration groups over the 17-day assessment period. Only cells incubated with Omniscan and Teslascan differed from the other groups on days 3 and 7 postincubation (P < 0.05). After day 7, a cell regain occurred in the Omniscan and Teslascan groups reaching the numbers of the other groups in sequel. Differences in colony formation were consistent with PK results with a statistically significant reduction in clonogenic activity for Teslascan and Omniscan in HUVEC cells, P < 0.05. No reduction in viability was seen for all groups and conditions. TGF-beta expression of HSF cells incubated with 1x concentration and all CM did not differ significantly from control cells for any point in time investigated. At 20x concentration directly after incubation, TGF-beta was significantly reduced for the Teslascan and Resovist group as 3 compared with control and all other CM groups, P < 0.05. On day 3 postincubation, only Resovist-incubated HSF cells showed a significant reduction of TGF-beta (1.614, standard deviations: 89) as compared with the control group (2.883, standard deviations: 30) and the other CM. TGF-beta was slightly reduced for all CM groups 8 days after incubation (not statistically significant, P > 0.05). CONCLUSIONS: After 24 hours of incubation with Omniscan and Teslascan (10x and 20x concentration), considerable short-term antiproliferative effects in HUVECs were observed. HSF cells (20x concentration) showed a reduction of TGF-beta for Resovist and Teslascan directly after incubation, whereas TGF-beta levels in HSF cells were slightly reduced for all CM 8 days after incubation. Therefore, TGF-beta-mediated proliferative effects on fibroblasts or on collagen synthesis potentially leading to nephrogenic systemic fibrosis may mainly be triggered by tissue monocytes and macrophages in the peripheral blood instead of dermal fibroblasts.
机译：理由和目的：这项研究的目的是评估6种市售磁共振造影剂（CM）对人脐静脉内皮细胞（HUVEC）的影响以及在皮肤成纤维细胞中诱导转化生长因子-β（TGF-β）的作用。 （HSF）作为肾源性系统性纤维化发病机制的可能模型。方法：使用基于g的CM Gadovist，Magnevist，Multihance和Omniscan，将HUVEC与CM应用达到的10x和20x摩尔标准血药浓度进行磁共振成像检查（10x和20x浓度）孵育24小时。 Teslascan（基于锰）和Resovist（基于铁）。进行增殖动力学（PK），菌落形成和生存力测定。此外，将人皮肤成纤维细胞（HSF）在所有6 CM中分别以1x和20x浓度孵育24小时，并在孵育期后以及孵育后第3和8天直接评估TGF-β水平。结果：HUVEC PK数据显示，在17天的评估期内，两个浓度组中所有6 CM的细胞数量都有相似的增加。在孵育后第3天和第7天，只有用Omniscan和Teslascan孵育的细胞不同于其他组（P <0.05）。第7天后，Omniscan和Teslascan组发生了细胞恢复，并达到了续集中其他组的数目。集落形成的差异与PK结果一致，在HUVEC细胞中对Tessscan和Omniscan的克隆形成活性统计上显着降低，P ＜0.05。在所有组和条件下均未观察到生存力降低。在研究的任何时间点，以1x浓度孵育的HSF细胞的TGF-β表达和所有CM与对照细胞均无显着差异。孵育后直接以20x的浓度，与对照组和所有其他CM组相比，Teslascan和Resovist组的TGF-β显着降低为3，P <0.05。孵育后第3天，与对照组（2.883，标准偏差：30）和其他CM相比，只有Resovist孵育的HSF细胞显示出TGF-beta的显着降低（1.614，标准偏差：89）。孵育8天后，所有CM组的TGF-beta均略有降低（无统计学意义，P> 0.05）。结论：在与Omniscan和Teslascan（浓度分别为10x和20x）温育24小时后，观察到HUVEC具有相当的短期抗增殖作用。孵育后，HSF细胞（浓度为20x）显示Resovist和Teslascan的TGF-β降低，而孵育8天后，所有CM的HSF细胞中TGF-β的含量均略有降低。因此，TGF-β介导的对成纤维细胞或胶原蛋白合成的增殖作用可能会导致肾原性系统性纤维化，其可能主要由外周血中的组织单核细胞和巨噬细胞而非真皮成纤维细胞触发。

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