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Study Of Important Signal Pathway In Inflammation And Thrombosis

Posted on:2008-05-31Degree:DoctorType:Dissertation
Country:ChinaCandidate:J T WangFull Text:PDF
GTID:1104360215455111Subject:Biochemistry and Molecular Biology
Abstract/Summary:PDF Full Text Request
NF-κB plays important roles in inflammation and thrombosis. However, the detailed mechanisms by which NF-κB controls thrombosis have not been completely understood. We demonstrated here that NF-κB transcription factor p50 critically regulated the expression of TF gene in the pathogeneses of deep vein thrombosis and arterial restenosis. Specific inhibition of p50 transcription factor by Andro or mutating of p50 in mice suppressed the expression of TF and other pro-inflammation factors, and resulted in reduced venous thrombosis and decreased neointimal hyperplasia.The binding of P-Selectin to its receptor, PSGL-1, mediated the activation of integrin, but the signal transducion pathway and importance of the binding in inflammation has not been studied yet. Our studies for the first time demonstrated the biological significance of selectin-mediated priming of leukocytes for integrin activation in vivo. P-selectin is fundamentally involved in the initial stage of leukocyte adhesion for the eventual accumulation of leukocytes at sites of inflammation. The polypeptide containing encoding Tat-PSGL-1 cytoplasmic tail abolished leukocyte adhesion and attenuated peritoneal deposition of leukocytes. These results indicate that P-selectin is not only an adhesion molecule but also signaling molecule mediating integrin activation.
Keywords/Search Tags:p50, thrombosis, P-selectin, PSGL-1, integrin
PDF Full Text Request
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