Rapid change of glucose concentration promotes mesangial cell proliferation via VEGF: inhibitory effects of thiazolidinedione
Rapid change of glucose concentration promotes mesangial cell proliferation via VEGF: inhibitory effects of thiazolidinedione
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DOI：
10.1016/j.bbrc.2004.02.175
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发表时间：
2004-04-23
影响因子：
3.1
通讯作者：
Watanabe, T
中科院分区：
文献类型：
--
作者：
Onozaki, A;Midorikawa, S;Watanabe, T
糖尿病肾病是糖尿病常见的并发症。噻唑烷二酮（TZD）被认为可以改善糖尿病肾病，但其机制尚未阐明。我们推测VEGF参与了糖尿病肾病的发病机制，TZD可能通过其对VEGF的作用而有益于糖尿病肾病的治疗。糖尿病大鼠肾小球和高糖培养的大鼠系膜细胞（RMC）中VEGF表达增加。VEGF可促进系膜细胞增殖，TZD可抑制系膜细胞增殖。结果表明，环境葡萄糖浓度的快速下降和上升诱导更多的VEGF的生产和细胞增殖RMC比在细胞与连续高糖培养基，这也被TZD抑制。前列腺素J2和蛋白C激酶抑制剂显着抑制[H-3]胸苷掺入与VEGF，TZD抑制RMC。这些发现表明，葡萄糖浓度的快速变化通过增加VEGF的产生促进RMC增殖。TZD至少部分通过PPAR-gamma发挥抑制作用。(C)2004年爱思唯尔公司All rights reserved.
Diabetic nephropathy is a common complication in diabetes mellitus (DM). Thiazolidinedione (TZD) is thought to ameliorate diabetic nephropathy, however, the mechanism has not been elucidated. We hypothesized that VEGF participates in the pathogenesis of diabetic nephropathy and that TZD may be beneficial for the treatment of diabetic nephropathy through its effect on VEGF. Increased VEGF expression was demonstrated in the glomeruli of DM rats and rat mesangial cells (RMC) incubated with high medium glucose. It was also demonstrated that VEGF promoted mesangial cell proliferation, which was inhibited by TZD. It was shown that a rapid fall and rise of ambient glucose concentration induces more VEGF production and cell proliferation in RMC than in cells with continuously high glucose medium, which was also inhibited by TZD. Prostaglandin J2 and protein C kinase inhibitors significantly inhibited [H-3]thymidine incorporation in RMC incubated with VEGF, which was inhibited by TZD. These findings indicate that a rapid change of glucose concentration promotes RMC proliferation by the increased Production of VEGF. TZD has an inhibitory action through, at least in part, PPAR-gamma. (C) 2004 Elsevier Inc. All rights reserved.