Enamel matrix derivative induces production of vascular endothelial cell growth factor in human gingival fibroblasts
Enamel matrix derivative induces production of vascular endothelial cell growth factor in human gingival fibroblasts
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DOI：
10.1111/j.1600-0722.2012.00999.x
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发表时间：
2012-12-01
影响因子：
1.9
通讯作者：
Noguchi, Kazuyuki
中科院分区：
文献类型：
--
作者：
Sakoda, Kenji;Nakajima, Yumiko;Noguchi, Kazuyuki
牙釉质基质衍生物（EMD）可能通过诱导血管生成促进牙周创伤愈合。我们试图研究EMD对人牙龈成纤维细胞产生血管内皮生长因子（VEGF）的影响和作用机制。用EMD、转化生长因子-β 1（TGF-β 1）或成纤维细胞生长因子2（FGF-2）刺激细胞，有或没有TGF-β 1或FGF-2的抗体。使用ELISA测量培养基中VEGF的水平。我们检测了SB 203580 [一种p38丝裂原活化蛋白激酶（MAPK）抑制剂]、U 0126 [一种细胞外信号调节激酶（ERK）抑制剂]、SP 600125 [一种c-Jun N-末端激酶（JNK）抑制剂]和LY 294002 [一种磷脂酰肌醇3-激酶（PI 3 K）/Akt抑制剂]对EMD诱导的VEGF产生的影响。牙釉质基质衍生物刺激VEGF的产生在剂量和时间依赖性的方式。用TGF-β 1或FGF-2抗体处理人牙龈成纤维细胞显著降低EMD诱导的VEGF产生，而加入外源性TGF-β 1和FGF-2刺激VEGF产生。SB 203580、U 0126和LY 294002显著减弱釉质基质衍生物诱导的VEGF产生。我们的研究结果表明，EMD刺激VEGF的生产，部分通过TGF-β 1和FGF-2在人牙龈成纤维细胞和EMD诱导的VEGF的生产是由ERK，p38 MAPK，PI 3 K/Akt途径调节。牙釉质基质衍生物诱导人牙龈成纤维细胞产生VEGF可能通过诱导血管生成参与促进牙周创伤愈合。
Enamel matrix derivative (EMD) may enhance periodontal wound healing by inducing angiogenesis. We sought to investigate the effect and the mechanism of action of EMD on vascular endothelial growth factor (VEGF) production by human gingival fibroblasts. Cells were stimulated with EMD, transforming growth factor-beta 1 (TGF-beta 1), or fibroblast growth factor 2 (FGF-2), with or without antibodies to TGF-beta 1 or FGF-2. The levels of VEGF in the culture media were measured using an ELISA. We examined the effects of SB203580 [a p38 mitogen-activated protein kinase (MAPK) inhibitor], U0126 [an extracellular signal-regulated kinase (ERK) inhibitor], SP600125 [a c-Jun N-terminal kinase (JNK) inhibitor], and LY294002 [a phosphatidylinositol 3-kinase (PI3K)/Akt inhibitor] on EMD-induced VEGF production. Enamel matrix derivative stimulated the production of VEGF in a dose- and time-dependent manner. Treatment of human gingival fibroblasts with antibodies to TGF-beta 1 or FGF-2 significantly decreased EMD-induced VEGF production, whereas the addition of exogenous TGF-beta 1 and FGF-2 stimulated VEGF production. Enamel matrix derivative-induced VEGF production was significantly attenuated by SB203580, U0126, and LY294002. Our results suggest that EMD stimulates VEGF production partially via TGF-beta 1 and FGF-2 in human gingival fibroblasts and that EMD-induced VEGF production is regulated by ERK, p38 MAPK, and PI3K/Akt pathways. Enamel matrix derivative-induced production of VEGF by human gingival fibroblasts may be involved in the enhancement of periodontal wound healing by inducing angiogenesis.