Role of p21-activated kinase 1 in regulating the migration and invasion of fibroblast-like synoviocytes from rheumatoid arthritis patients
作者： D. Fu , Y. Yang , Y. Xiao , H. Lin , Y. Ye
DOI: 10.1093/RHEUMATOLOGY/KES031
关键词:
摘要: Objective. To investigate the role of p21-activated kinase 1 (PAK1) in regulating migration, invasion and MMP expression RA fibroblast-like synoviocytes (FLS). Methods. FLS migration vitro were measured by Boyden chamber method. Invasion into cartilage was detected severe combined immunodeficiency (SCID) mouse co-implantation model vivo. PAK1 MT1-MMP examined western blotting. ELISA used to measure production activity MMPs. Results. Phosphorylated (p-PAK1) protein increased ex vivo synovial membrane cells from patients. Stimulation with IL-1b or TNF-a up-regulated p-PAK1 expression. Inhibition transfection dominant negative mutant (dnPAK1) reduced FLS. In SCID model, attenuated dnPAK1 regulated IL-1b-induced MMP-13 MT1-MMP. also invasion. Furthermore, inhibited c-Jun N-terminal (JNK) activation, but did not affect activities extracellular signal-regulated kinases p38. JNK chemical inhibitor significantly
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