The Study Of The Effect Of Focal Adhesion Kinase (FAK) And P53 In Rheumatoid Arthritis Fibroblast Like Synoviocytes On Cell Proliferation

Background:Rheumatoid arthritis(RA) is a systemic autoimmune disease characterized by chronic and erosive synovitis. It can affect multiple joints leading to its destruction,deformation, and eventually leading to physical disability, and has brought great suffering to the patient. The world-wide prevalence of RA ranges from 0.5% to 1%.Numerous studies show that fibroblast like synoviocytes(FLS) over proliferation is the key to the pathogenesis of RA. Focal adhesion kinase(FAK) is a protein kinase, and it plays an important role in intracellular signal transduction. The study of tumors showed that FAK can suppress apoptosis by it’s FERM domain of the N-terminal binding with p53. So FAK can inhibit the expression of p53 gene then lead to the occurrence of tumor.There are reports indicating that RA FLS share many similar properties with tumor cells,such as undergoing tumor-like proliferation, migration and invasion. And the mechanism may be similar to it in proliferation and metastasis of tumor cells. Our early studies have shown that the expression of FAK in RA synovial tissue was significantly higher than the normal synovial tissue, and after treatment the expression can be inhibited. This suggests that FAK plays an important role in the process of FLS proliferation. Researches show that, the deletion of p53 may be involved in the pathological process of FLS proliferation.So in the pathogenesis of RA, whether FAK can interaction with p53 to reduce the excessive proliferation of FLS or not is worth studying.Objective:(1). Observe the expression of FAK and p53 in RA Fibroblast Like Synoviocytes,and investigate the pathogenesis of RA;(2). Discuss the effect of FAK and p53 on the proliferation of Fibroblast Like Synoviocytes in RA, provide a new target for the treatment of RA.Methods:(1). Culture synovial tissue from RA patients in vitro;(2). FLS are cultured in TNF-α(10ng/ml) and different density protease inhibitor(MG-132)(1μM、5μM、10μM、20μM) for 48 h then we detect the level of m RNA both of FAK and p53 in each group by RT-PCR;(3). FLS are cultured in different density protease inhibitor(MG-132)(1μM、5μM、10μM、20μM)for 24h、48h、72h、96h then we detect the cell proliferation of each group;(4). Analysis data by SPSS 17 statistical software.Results:(1). After TNF-α stimulating, the level of FAK m RNA was higher than control group(P<0.05); there is no difference between TNF-αgroup and control group in the level of p53 m RNA(P>0.05).(2). After different density MG-132 stimulating, the level of p53 m RNA was higher than control group(P<0.05), and the 5μM group is the highest of them; there is no difference between MG-132 group and control group in the level of FAK m RNA(P>0.05).(3). After different density MG-132 stimulating, the proliferation of FLS is slower than control group(P<0.05).Conclusions:(1). In vitro, After TNF-α stimulating, the level of m RNA of Focal adhesion kinase increased, while the level of that decreased after MG-132 stimulating. Focal adhesion kinase involved in the pathogenesis of rheumatoid arthritis.(2). In vivo, after MG-132 stimulating, the level of m RNA of p53 increased. p53 can inhibit the excessive proliferation of rheumatoid arthritis synovial fibroblast cells and plays an important role in the pathogenesis of rheumatoid arthritis.