Fibroblast response to gadolinium: role for platelet-derived growth factor receptor.

Abstract:

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.

journal_name

Invest Radiol

journal_title

Investigative radiology

authors

Bhagavathula N,Dame MK,DaSilva M,Jenkins W,Aslam MN,Perone P,Varani J

doi

10.1097/RLI.0b013e3181e943d2

subject

Has Abstract

pub_date

2010-12-01 00:00:00

pages

769-77

issue

12

eissn

0020-9996

issn

1536-0210

journal_volume

45

pub_type

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