Search Results (2)

Osteopontin (OPN), a matricellular protein, is produced as a full-length OPN (FL-OPN) and cleaved by thrombin, thus generating the N-terminal half of OPN (OPN N-half) with new functions. Although plasma FL-OPN levels have been associated with neurovascular events after aneurysmal subarachnoid hemorrhage (SAH), plasma OPN N-half levels have never been investigated. In this study, prospective clinical data and plasma samples were collected from 108 consecutive SAH patients with ruptured aneurysms undergoing acute treatment via surgery, and FL-OPN and OPN N-half levels were measured in plasma with a particular focus on delayed cerebral infarction (DCIn), which has the greatest impact on outcomes. Plasma FL-OPN and OPN N-half levels were intercorrelated and significantly higher in patients with DCIn at days 10–12 post-SAH; a greater area under the receiver-operating characteristic curve was observed for OPN N-half levels, with a cut-off value of 70.42 pmol/L. Multivariate analyses revealed that plasma OPN N-half levels of ≥70.42 pmol/L at days 10–12 were independently associated with DCIn development (adjusted odds ratio, 5.65; 95% confidence interval, 1.68–18.97; p = 0.005). Based on the findings of this study and previous reports, an increase in the OPN N-half level may be indicative of a protective mechanism against DCIn development, and, thus, it holds promise as a new therapeutic target against DCIn after aneurysmal SAH. Full article

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. Full article