Fibroblast response to gadolinium: role for platelet-derived growth factor receptor.
Fibroblast response to gadolinium: role for platelet-derived growth factor receptor.
复制标题
DOI：
10.1097/rli.0b013e3181e943d2
复制
发表时间：
2010-12
影响因子：
6.7
通讯作者：
Varani J
中科院分区：
文献类型：
--
作者：
Bhagavathula N;Dame MK;DaSilva M;Jenkins W;Aslam MN;Perone P;Varani J
本研究的目的是评估钆（Gd 3+）（以氯化钆形式提供）对成纤维细胞功能的影响。将单层培养中的人真皮成纤维细胞和器官培养中的完整皮肤暴露于镧系金属（1-20 μM）。观察到增殖增加，与基质金属蛋白酶-1（MMP-1）和金属蛋白酶组织抑制剂-1（TIMP-1）的上调相关，而I型前胶原的产生没有明显增加。PDGF受体阻断抗体抑制响应于Gd 3+的成纤维细胞增殖，信号传导途径的抑制剂也是如此-即，丝裂原活化蛋白（MAP）激酶和磷脂酰肌醇-3（PI 3）激酶途径-由PDGF激活。对氯化钆的反应与先前在临床使用的MRI造影剂中使用螯合Gd 3+观察到的反应相似。成纤维细胞反应似乎反映了Gd 3+诱导的PDGF受体活化和下游信号传导。真皮成纤维细胞增殖增加以及对MMP-1和TIMP-1的影响可能有助于在肾源性系统性纤维化个体的病变皮肤中观察到的纤维增生/纤维化变化。
The purpose of this study was to assess the effects of gadolinium (Gd3+), provided as gadolinium chloride, on fibroblast function. Human dermal fibroblasts in monolayer culture and intact skin in organ culture were exposed to the lanthanide metal (1-20 μM). Increased proliferation was observed, in association with up-regulation of matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinases-1 (TIMP-1), without an apparent increase in production of type I procollagen. A PDGF receptor-blocking antibody inhibited fibroblast proliferation in response to Gd3+ as did inhibitors of signaling pathways – i.e., mitogen-activated protein (MAP) kinase and phosphatidylinositol-3 (PI3) kinase pathways – that are activated by PDGF. The responses to gadolinium chloride are similar to responses previously seen with chelated Gd3+ in clinically-used MRI contrast agents. Fibroblast responses appear to reflect Gd3+ - induced PDGF receptor activation and down-stream signaling. Increased dermal fibroblast proliferation in conjunction with effects on MMP-1 and TIMP-1 could contribute to the fibroplastic / fibrotic changes seen in the lesional skin of individuals with nephrogenic systemic fibrosis.