High glucose upregulates connective tissue growth factor expression in human vascular smooth muscle cells.
High glucose upregulates connective tissue growth factor expression in human vascular smooth muscle cells.
复制标题
DOI：
10.1186/1471-2121-8-1
复制
发表时间：
2007-01-16
期刊：
影响因子：
--
通讯作者：
Chen, Huaiqing
中科院分区：
文献类型：
--
作者：
Liu, Xiaojing;Luo, Fengming;Pan, Kejian;Wu, Wenchao;Chen, Huaiqing
结缔组织生长因子 (CTGF) 是一种有效的促纤维化因子，与成纤维细胞增殖、血管生成和细胞外基质 (ECM) 合成有关。它是转化生长因子 β (TGFβ) 某些效应的下游介质，可能由人肾系膜细胞中的高血糖诱导。然而，高糖是否会诱导血管平滑肌细胞（VSMC）中CTGF的表达仍不清楚。因此，本研究旨在测试高葡萄糖是否可以调节人VSMC中CTGF的表达。进一步研究了调节CTGF表达对VSMC增殖和迁移的影响。在暴露于高葡萄糖条件后，培养的人 VSMC 中 CTGF mRNA 的表达早在 6 小时就上调，随后 ECM 成分（I 型胶原和纤连蛋白）积累。 CTGF mRNA 的上调似乎依赖于 TGFβ，因为抗 TGFβ 抗体可阻断高葡萄糖对 CTGF 基因表达的影响。靶向 CTGF mRNA (CTGF-siRNA) 的小干扰 RNA (siRNA) 有效抑制高葡萄糖刺激的 CTGF 上调，抑制率高达 79%。由于CTGF基因表达减少，VSMC中ECM蛋白的沉积也减少。此外，CTGF-siRNA表达载体部分抑制高糖诱导的VSMC增殖和迁移。我们的数据表明，在糖尿病大血管并发症的发展过程中，CTGF可能是参与人类VSMC对高葡萄糖病理生理反应的重要因素。此外，CTGF-siRNA在此过程中的调节作用表明，通过RNA干扰特异性靶向CTGF可能有助于预防糖尿病大血管并发症中的内膜增生。
Connective tissue growth factor (CTGF) is a potent profibrotic factor, which is implicated in fibroblast proliferation, angiogenesis and extracellular matrix (ECM) synthesis. It is a downstream mediator of some of the effects of transforming growth factor β (TGFβ) and is potentially induced by hyperglycemia in human renal mesangial cells. However, whether high glucose could induce the CTGF expression in vascular smooth muscle cells (VSMCs) remains unknown. Therefore, this study was designed to test whether high glucose could regulate CTGF expression in human VSMC. The effect of modulating CTGF expression on VSMC proliferation and migration was further investigated. Expression of CTGF mRNA was up-regulated as early as 6 hours in cultured human VSMCs after exposed to high glucose condition, followed by ECM components (collagen type I and fibronectin) accumulation. The upregulation of CTGF mRNA appears to be TGFβ-dependent since anti-TGFβ antibody blocks the effect of high glucose on CTGF gene expression. A small interference RNA (siRNA) targeting CTGF mRNA (CTGF-siRNA) effectively suppressed CTGF up-regulation stimulated by high glucose up to 79% inhibition. As a consequence of decreased expression of CTGF gene, the deposition of ECM proteins in the VSMC was also declined. Moreover, CTGF-siRNA expressing vector partially inhibited the high glucose-induced VSMC proliferation and migration. Our data suggest that in the development of macrovascular complications in diabetes, CTGF might be an important factor involved in the patho-physiological responses to high glucose in human VSMCs. In addition, the modulatory effects of CTGF-siRNA during this process suggest that specific targeting CTGF by RNA interference could be useful in preventing intimal hyperplasia in diabetic macrovascular complications.
登录
查看更多内容
影响因子：
4.8
作者：
Fan, WH;Karnovsky, MJ
通讯作者：
Karnovsky, MJ
DOI：
10.1161/01.atv.0000092913.60428.e6
发表时间：
2003-10-01
影响因子：
8.7
作者：
Iwanciw, D;Rehm, M;Goppelt-Struebe, M
通讯作者：
Goppelt-Struebe, M
影响因子：
5.6
作者：
Chujo, S;Shirasaki, F;Takehara, K
通讯作者：
Takehara, K
影响因子：
11.2
作者：
Croci, S;Landuzzi, L;Lollini, PL
通讯作者：
Lollini, PL
影响因子：
2.3
作者：
Kobayashi, Tatsuya;Inoue, Tsutomu;Suzuki, Hiromichi
通讯作者：
Suzuki, Hiromichi