Up-regulation of vascular endothelial growth factor in synovial fibroblasts from human temporomandibular joint by hypoxia
Up-regulation of vascular endothelial growth factor in synovial fibroblasts from human temporomandibular joint by hypoxia
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DOI：
10.1111/j.1600-0714.2007.00532.x
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发表时间：
2007-05-01
影响因子：
3.3
通讯作者：
Zhang, Yufeng
中科院分区：
文献类型：
--
作者：
Ke, Jin;Liu, Yu;Zhang, Yufeng
引言：血管内皮生长因子（VEGF）的表达增强已被描述在内部紊乱（ID）患者。在此，我们研究了VEGF在颞下颌关节（TMJ）滑膜成纤维细胞在缺氧条件下的表达，并探讨了缺氧诱导因子-I α（HIF-I α）参与VEGF表达的调节。将这些细胞在低氧或常氧下孵育指定的时间段。通过ELISA测量培养上清液中的VEGF水平。RT-PCR和北方印迹分析检测VEGF mRNA亚型和稳定性。结果：低氧可诱导滑膜成纤维细胞表达VEGF，且VEGF的表达量随低氧浓度的增加而增加。缺氧后VEGF 121和VEGF 165 mRNA表达均显著增加，而VEGFmRNA的稳定性无明显变化。结论：低氧可能主要通过诱导滑膜成纤维细胞表达VEGF 121和VEGF 165促进TMJ炎症血管生成。HIF-1 α在缺氧时明显激活，可能控制TMJ滑膜成纤维细胞VEGF的表达。
INTRODUCTION: Enhanced expression of vascular endothelial growth factor (VEGF) has been described in patients with internal derangement (ID). Herein, we examined the expression of VEGF in synovial fibroblasts from temporomandibular joint (TMJ) under hypoxia and investigated the regulation of hypoxia-inducible factor-I alpha (HIF-I alpha) involved in the expression of VEGF.METHODS: Synovial fibroblasts were prepared from human TMJ. These cells were incubated under hypoxia or normoxia for the indicated time periods. VEGF levels in cultured supernatant were measured by an ELISA. VEGF mRNA isoforms and stability were assessed using RTPCR and Northern blot analysis respectively. HIF-I alpha accumulation was evaluated by Western blotting and immunofluorescence.RESULTS: VEGF were significantly induced by hypoxia in synovial fibroblasts. In response to hypoxia, VEGF 121 and VEGF165 mRNA were both remarkably increased, while there was no change in VEGF mRNA stability. The accumulation and nuclear translocation of HIF-I alpha occurred under hypoxia.CONCLUSIONS: Hypoxia may mainly induce the expression of VEGF121 and VEGF 165 in synovial fibroblasts to promote inflamed angiogenesis of TMJ. HIF-I alpha, which is clearly activated in response to hypoxia, may control the expression of VEGF in synovial fibroblasts from TMJ.