Activation of Ras/MEK/ERK signaling in chronic subdural hematoma outer membranes.
Chronic subdural hematoma (CSDH) is considered to be an angiogenic disease. Vascular endothelial growth factor (VEGF), one of the important growth factors regulating angiogenesis, is expressed in the neomembranes and also in hematoma fluid, and the Ras/MEK/ERK signaling pathway has been implicated in angiogenesis by VEGF. In the present study, the status of this signaling pathway in CSDH outer membranes was examined using outer membranes obtained during trepanation surgery. The expression levels of Ras, Ras-GAP, c-Raf, MEK, ERK, phosphorylated (p)-ERK, endothelial nitric oxide synthase (eNOS) and actin were examined by western blot analysis; the expression of p-ERK was also examined by immunohistochemistry. Ras, Ras-GAP, c-Raf, MEK, ERK and eNOS were detected in all cases. In addition, the expression of p-ERK was confirmed in all cases, and p-ERK was localized to the endothelial cells of the vessels in CSDH outer membranes. These findings indicated that Ras/MEK/ERK signaling is activated in the CSDH outer membranes and suggested the possibility that the Ras/MEK/ERK pathway might be activated by VEGF and play a critical role in the angiogenesis of CSDHs.
Department of Neurological Surgery, Aichi Medical University, 1-1 Yazakokarimata, Nagakute, Aichi 480-1195, Japan. kosuka@aichi-med-u.ac.jp
Koji
K
Osuka
Yasuo
Y
Watanabe
Nobuteru
N
Usuda
Kimie
K
Atsuzawa
Masahiro
M
Aoyama
Aichi
A
Niwa
Takahiro
T
Nakura
Masakazu
M
Takayasu
D000368:Aged; D002560:Cerebrovascular Circulation / Q000502:physiology; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D020200:Hematoma, Subdural, Chronic / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010766:Phosphorylation / Q000502:physiology; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D020703:ras GTPase-Activating Proteins / Q000378:metabolism
C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D020703:ras GTPase-Activating Proteins; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D019908:Proto-Oncogene Proteins c-raf; D016283:Proto-Oncogene Proteins p21(ras)