The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201210, China.
J Biochem. 2011 Aug;150(2):189-97. doi: 10.1093/jb/mvr060. Epub 2011 May 13.
Angiogenesis, the process of new blood vessels formation, is a critical step for wound healing, tumour growth and metastasis, diabetic retinopathy, psoriasis, etc. The present study was designed to investigate whether c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) is critical for regulating basic fibroblastic growth factor (bFGF)-induced angiogenesis in human umbilical vein endothelial cells (HUVECs). Our results showed that bFGF-induced HUVECs proliferation, migration and tube formation with a concentration-dependent manner. Further results showed that bFGF induced the phosphorylation of JNK/SAPK at 15 min. Both JNK/SAPK inhibitor SP600125 and JNK/SAPK peptide inhibitor 420116 could inhibit bFGF-induced HUVECs proliferation, migration and tube formation, so did JNK/SAPK-specific siRNA. Moreover, when HUVECs were stimulated with bFGF, upstream signals of JNK/SAPK, SEK1/MKK4 and MKK7 were both activated at 2 min. In summary, our results indicate that JNK/SAPK signal pathway plays an important role in regulating bFGF-mediated angiogenesis in HUVECs, which may therefore be a new therapeutic approach for the treatment of angiogenesis-associated diseases.
血管生成，即新血管形成的过程，是创伤愈合、肿瘤生长和转移、糖尿病性视网膜病变、银屑病等的关键步骤。本研究旨在探讨 c-Jun N 端激酶/应激激活蛋白激酶（JNK/SAPK）是否对调节碱性成纤维细胞生长因子（bFGF）诱导的人脐静脉内皮细胞（HUVEC）血管生成至关重要。我们的结果表明，bFGF 以浓度依赖性方式诱导 HUVEC 增殖、迁移和管状结构形成。进一步的结果表明，bFGF 在 15 分钟诱导 JNK/SAPK 磷酸化。JNK/SAPK 抑制剂 SP600125 和 JNK/SAPK 肽抑制剂 420116 均可抑制 bFGF 诱导的 HUVEC 增殖、迁移和管状结构形成，JNK/SAPK 特异性 siRNA 也有同样作用。此外，当 HUVEC 受到 bFGF 刺激时，JNK/SAPK 的上游信号 SEK1/MKK4 和 MKK7 在 2 分钟时均被激活。总之，我们的结果表明，JNK/SAPK 信号通路在调节 bFGF 介导的 HUVEC 血管生成中起重要作用，因此可能成为治疗与血管生成相关疾病的新方法。
