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Involvement of c-Jun N-terminal kinase and extracellular signal-regulated kinase 1/2 in EGF-induced angiogenesis

Authors

  • Kaikai Shen,

    1. 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, Peoples Republic of China
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  • Yuchen Sheng,

    1. Department of Pharmacology, Shanghai Institute of Pharmaceutical Industry, Shanghai 200437, Peoples Republic of China
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  • Lili Ji,

    Corresponding author
    1. 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, Peoples Republic of China
    2. Shanghai RD Centre for Standardization of Chinese Medicines, Shanghai 201210, Peoples Republic of China
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  • Zhengtao Wang

    1. 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, Peoples Republic of China
    2. Shanghai RD Centre for Standardization of Chinese Medicines, Shanghai 201210, Peoples Republic of China
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To whom correspondence should be addressed (email lily0913@yahoo.cn).

Abstract

Angiogenesis is a process during which endothelial cells divide and migrate to form new capillaries from the preexisting blood vessels. The present study was designed to investigate whether MAPKs (mitogen-activated protein kinases) play crucial roles in regulating EGF (epidermal growth factor)-induced endothelial cell angiogenesis. Our results showed that EGF stimulated HUVEC (human umbilical vein endothelial cells) proliferation in a concentration-dependent manner, of which the maximum effective concentration of EGF was 10 ng/ml. Western blot analysis showed that EGF at 10 ng/ml significantly induced the phosphorylation of ERK1/2 (extracellular signal-regulated kinase 1 and 2) and p38 kinase at 5 min, while it induced the phosphorylation of JNK/SAPK (c-Jun N-terminal kinase/stress-activated protein kinase) at 15 min. Further results showed that a JNK/SAPK inhibitor, SP600125, and a specific siRNA JNK/SAPK could both significantly inhibit EGF-induced tube formation in HUVEC cells, and an ERK1/2 inhibitor PD098059 could also block the tube formation in some content, while a p38 inhibitor SB203580 failed to do so. Furthermore, only SP600125 significantly inhibited EGF-induced HUVEC cell proliferation under no cytotoxic concentration, so did JNK/SAPK siRNA. In conclusion, JNK/SAPK and ERK1/2 signals therefore play critical roles in EGF-mediated HUVEC cell angiogenesis.

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