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 upregulation of matrix metalloproteinase-1 and tissue inhibitor of metalloproteinases-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 Gd3+ as did inhibitors of signaling pathways--that is, mitogen-activated protein kinase and phosphatidylinositol-3 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 magnetic resonance imaging contrast agents. Fibroblast responses appear to reflect Gd3+-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.
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 lanthanidemetal (1-20 μM). RESULTS: Increased proliferation was observed, in association with upregulation of matrix metalloproteinase-1 and tissue inhibitor of metalloproteinases-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 Gd3+ as did inhibitors of signaling pathways--that is, mitogen-activated protein kinase and phosphatidylinositol-3 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 magnetic resonance imaging contrast agents. Fibroblast responses appear to reflect Gd3+-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.
Authors: A Luana Stanescu; Dennis W Shaw; Nozomu Murata; Kiyoko Murata; Joe C Rutledge; Ezekiel Maloney; Kenneth R Maravilla Journal: Pediatr Radiol Date: 2020-01-27
Authors: William Jenkins; Patricia Perone; Kyle Walker; Narasimharao Bhagavathula; Muhammad Nadeem Aslam; Marissa DaSilva; Michael K Dame; James Varani Journal: Biol Trace Elem Res Date: 2011-04-12 Impact factor: 3.738
Authors: N Fretellier; Jm Idée; P Bruneval; S Guerret; F Daubiné; G Jestin; C Factor; N Poveda; A Dencausse; F Massicot; O Laprévote; C Mandet; N Bouzian; M Port; C Corot Journal: Br J Pharmacol Date: 2012-02 Impact factor: 8.739