학술논문
Angiogenesis in the Outer Membrane of Chronic Subdural Hematomas through Thrombin-Cleaved Osteopontin and the Integrin α9 and Integrin β1 Signaling Pathways.
Document Type
Academic Journal
Author
Osuka K; Department of Neurological Surgery, Aichi Medical University, 1-1 Yazakokarimata, Nagakute 480-1195, Japan.; Ohmichi Y; Department of Anatomy II, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Kahoku 920-0293, Japan.; Ohmichi M; Department of Anatomy II, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Kahoku 920-0293, Japan.; Honma S; Department of Anatomy II, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Kahoku 920-0293, Japan.; Suzuki C; Department of Neurological Surgery, Aichi Medical University, 1-1 Yazakokarimata, Nagakute 480-1195, Japan.; Aoyama M; Department of Neurological Surgery, Aichi Medical University, 1-1 Yazakokarimata, Nagakute 480-1195, Japan.; Iwami K; Department of Neurological Surgery, Aichi Medical University, 1-1 Yazakokarimata, Nagakute 480-1195, Japan.; Watanabe Y; High Technology Research Center, Pharmacology, Showa Pharmaceutical University, 3-3165 Higashi-Tamagawa Gakuen, Machida 194-8543, Japan.; Miyachi S; Department of Neurological Surgery, Aichi Medical University, 1-1 Yazakokarimata, Nagakute 480-1195, Japan.
Source
Publisher: MDPI AG Country of Publication: Switzerland NLM ID: 101691304 Publication Model: Electronic Cited Medium: Print ISSN: 2227-9059 (Print) Linking ISSN: 22279059 NLM ISO Abbreviation: Biomedicines Subsets: PubMed not MEDLINE
Subject
Language
English
ISSN
2227-9059
Abstract
Background: A chronic subdural hematoma (CSDH) is considered to be an inflammatory and angiogenic disease. The CSDH outer membrane, which contains inflammatory cells, plays an important role in CSDH development. Osteopontin (OPN) is an extracellular matrix protein that is cleaved by thrombin, generating the N-terminal half of OPN, which is prominently involved in integrin signal transduction. We explored the expression of the N-terminal half of OPN in CSDH fluid and the expression of integrins α9 and β1 and the downstream components of the angiogenic signaling pathways in the outer membrane of CSDHs.
Methods: Twenty samples of CSDH fluid and eight samples of CSDH outer membrane were collected from patients suffering from CSDHs. The concentrations of the N-terminal half of OPN in CSDH fluid samples were measured using ELISA kits. The expression levels of integrins α9 and β1, vinculin, talin-1, focal adhesion kinase (FAK), paxillin, α-actin, Src and β-actin were examined by Western blot analysis. The expression levels of integrins α9 and β1, FAK and paxillin were also examined by immunohistochemistry. We investigated whether CSDH fluid could activate FAK in cultured endothelial cells in vitro.
Results: The concentration of the N-terminal half of OPN in CSDH fluid was significantly higher than that in the serum. Western blot analysis confirmed the presence of these molecules. In addition, integrins α9 and β1, FAK and paxillin were localized in the endothelial cells of vessels within the CSDH outer membrane. FAK was significantly phosphorylated immediately after treatment with CSDH fluid.
Conclusion: Our data suggest that the N-terminal half of OPN in CSDH fluid promotes neovascularization in endothelial cells through integrins α9 and β1. The N-terminal half of OPN, which is part of the extracellular matrix, plays a critical role in the promotion of CSDHs.
Methods: Twenty samples of CSDH fluid and eight samples of CSDH outer membrane were collected from patients suffering from CSDHs. The concentrations of the N-terminal half of OPN in CSDH fluid samples were measured using ELISA kits. The expression levels of integrins α9 and β1, vinculin, talin-1, focal adhesion kinase (FAK), paxillin, α-actin, Src and β-actin were examined by Western blot analysis. The expression levels of integrins α9 and β1, FAK and paxillin were also examined by immunohistochemistry. We investigated whether CSDH fluid could activate FAK in cultured endothelial cells in vitro.
Results: The concentration of the N-terminal half of OPN in CSDH fluid was significantly higher than that in the serum. Western blot analysis confirmed the presence of these molecules. In addition, integrins α9 and β1, FAK and paxillin were localized in the endothelial cells of vessels within the CSDH outer membrane. FAK was significantly phosphorylated immediately after treatment with CSDH fluid.
Conclusion: Our data suggest that the N-terminal half of OPN in CSDH fluid promotes neovascularization in endothelial cells through integrins α9 and β1. The N-terminal half of OPN, which is part of the extracellular matrix, plays a critical role in the promotion of CSDHs.