Involvement of c-Jun N-terminal kinase and extracellular signal-regulated kinase 1/2 in EGF-induced angiogenesis.
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.
Shen
Kaikai
K
Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201210, Peoples Republic of China.
Sheng
Yuchen
Y
Ji
Lili
L
Wang
Zhengtao
Z
D002196:Capillaries / Q000187:drug effects / Q000254:growth & development; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism / Q000502:physiology*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism / Q000502:physiology*; D048055:Mitogen-Activated Protein Kinase 8 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D034741:RNA, Small Interfering / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
D034741:RNA, Small Interfering; D004815:Epidermal Growth Factor; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048055:Mitogen-Activated Protein Kinase 8