Objective
The purpose of this study was to assess the effects of gadolinium (Gd3+), 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 μM).
Results
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.
Conclusion
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.