Stimulation of fibroblast proliferation by insoluble gadolinium salts.
Stimulation of fibroblast proliferation by insoluble gadolinium salts.
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DOI：
10.1007/s12011-011-9176-9
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发表时间：
2012-02
影响因子：
3.9
通讯作者：
Varani, James
中科院分区：
文献类型：
--
作者：
Bleavins, Katherine;Perone, Patricia;Naik, Madhav;Rehman, Muneeb;Aslam, Muhammad N.;Dame, Michael K.;Meshinchi, Sasha;Bhagavathula, Narasimharao;Varani, James
关键词：
本研究的目的是评估含钆 (Gd3+) 的不溶性盐对人真皮成纤维细胞的影响。对不溶性 Gd3+ 盐的反应与用有机螯合剂溶解的 Gd3+ 所观察到的反应进行了比较，如用于磁共振成像的基于 Gd3+ 的造影剂 (GBCA)。 Gd3+-磷酸盐或Gd3+-碳酸盐的不溶性颗粒迅速附着在成纤维细胞表面并刺激增殖。在 12.5 至 125 μM 之间的 Gd3+ 浓度下观察到生长，在较高浓度下具有毒性。如此狭窄的窗口并不是 GBCA 刺激的特征。在有丝分裂原激活蛋白激酶和磷脂酰肌醇 3 激酶信号通路拮抗剂存在的情况下（与螯合 Gd3+ 类似），不溶性 Gd3+ 盐诱导的增殖受到抑制，但不会被血小板衍生生长因子受体抗体阻断（与螯合 Gd3+ 不同）。最后，高浓度的不溶性 Gd3+ 盐无法防止低 Ca2+ 条件下的成纤维细胞裂解，而类似浓度的螯合 Gd3+ 则有效。总之，虽然不溶性 Gd3+ 盐能够刺激成纤维细胞增殖，但应谨慎假设 GBCA 脱螯合必须在体内发生，才能在发生肾源性系统性纤维化的肾衰竭患者亚群中产生与 GBCA 暴露相关的促纤维化变化。
The purpose of this study was to assess insoluble salts containing gadolinium (Gd3+) for effects on human dermal fibroblasts. Responses to insoluble Gd3+ salts were compared to responses seen with Gd3+ solubilized with organic chelators, as in the Gd3+-based contrast agents (GBCAs) used for magnetic resonance imaging. Insoluble particles of either Gd3+-phosphate or Gd3+-carbonate rapidly attached to the fibroblast cell surface and stimulated proliferation. Growth was observed at Gd3+ concentrations between 12.5 and 125 μM, with toxicity at higher concentrations. Such a narrow window did not characterize GBCA stimulation. Proliferation induced by insoluble Gd3+ salts was inhibited in the presence of antagonists of mitogen-activated protein kinase and phosphatidylinositol 3-kinase signaling pathways (similar to chelated Gd3+) but was not blocked by an antibody to the platelet-derived growth factor receptor (different from chelated-Gd3+). Finally, high concentrations of the insoluble Gd3+ salts failed to prevent fibroblast lysis under low-Ca2+ conditions while similar concentrations of chelated-Gd3+ were effective. In conclusion, while insoluble Gd3+ salts are capable of stimulating fibroblast proliferation, one should be cautious in assuming that GBCA dechelation must occur in vivo to produce the profibrotic changes seen in association with GBCA exposure in the subset of renal failure patients that develop nephrogenic systemic fibrosis.
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影响因子：
6.7
作者：
Bhagavathula N;Dame MK;DaSilva M;Jenkins W;Aslam MN;Perone P;Varani J
通讯作者：
Varani J
影响因子：
2.9
作者：
Huang, Yun;Zhou, Yubin;Castiblanco, Adriana;Yang, Wei;Brown, Edward M.;Yang, Jenny J.
通讯作者：
Yang, Jenny J.
影响因子：
19.7
作者：
Collidge, Tara Anne;Thomson, Peter Campbell;Roditi, Giles Hannibal
通讯作者：
Roditi, Giles Hannibal
影响因子：
6.7
作者：
Bhagavathula N;DaSilva M;Aslam MN;Dame MK;Warner RL;Xu Y;Fisher GJ;Johnson KJ;Swartz R;Varani J
通讯作者：
Varani J
影响因子：
6.7
作者：
DaSilva M;O'Brien Deming M;Fligiel SE;Dame MK;Johnson KJ;Swartz RD;Varani J
通讯作者：
Varani J