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Objective To investigate the expression of fibroblast growth factor 4 (FGF4) in serum of active rheumatoid arthritis (RA) and its role in RA synoviocyte proliferation. Methods The serum level of FGF4 were detected by protein arrays in 20 patients with RA, and 20 age and gender matched healthy controls. FLSs were isolated from RA synovium,and were co-cultured with recombinant human FGF4 (rhFGF4). Cell proliferation was quantified by Cell Counting Kit-8 assay and cell cycle distribution was evaluated by flow-cytometry. The protein levels of cyclin D1, phospho-Akt (p-Akt) and phospho-p38 (p-p38) were measured by western blot. Results The serum expression of FGF4 in RA group was higher than that in control group (P=0.041). After being treated with different concentrations of rhFGF4 (12.5, 25, 50, and 100 ng/ml), RA-FLS showed significant increase in cell proliferation, with different rates of [(121 ±8)％], [(126 ±12)％], [(129 ± 12)％], a nd [(134 ±14)％] respectively, comparing with that of the controls [(100 ±0)％, (P12.5=0.049, P25=0.009, P50=0.004, P100=0.001).]. Among them, the percentage of G2/M+S phase cells were [(12.6±3.6)％], [(15.3±4.5)％], [(17.1±5.1)％], [(19.6±4.1)％] respectively, and except the lowest rhFGF4 concentration treatment group of 12.5 ng/ml, G2/M+S phase cells in other groups was significantly increased compared with the controls [(5.4±2.4)％] (P12.5=0.159, P25=0.042, P50=0.018, P100=0.005). And the protein expression of cyclin D1 was up-regulated after being treated with 50 ng/ml and 100 ng/ml rhFGF4 (P50=0.035, P100=0.027). FGF4 transiently increased the expression of p-Akt and p-p38 protein at the concentration of 50 ng/ml. Comparisons of data between groups were performed by independent sample Student's t-test. Statistical significant differences among groups were tested by one-way analysis of variance (ANOVA) or the Kruskal-Wallis test. The Dunnett's t-test was used for multiple comparisons. A P-value of <0.05 was considered statistically significant. Conclusion Our results suggest that FGF4 is highly expressed in the serum of active RA patients. FGF4 may promote the proliferation of RA-FLS via modulating PI3K/Akt and p38-MAPK signaling pathways, which subsequently contributs to synovial hyperplasia.
ABSTRACT
BACKGROUND:B cell activating factor belonging to tumor necrosis factor family(BAFF)is essential to B cell differentiation,maturation,survival,and antibody secretion via binding to its receptors,and may play a role in the development of T cell response.Whether or not BAFF signal participates in the kidney allograft rejection is worthy of studying.OBJECTIVE:To analyze the expression and potential bioactivity of BAFF in the peripheral lymphocytes of kidney transplant recipients.DESIGN,TIME AND SETTING:A case observation was performed at the Department of Urology,Third Affiliated Hospital of Soochow University from June 2006 to March 2007.PARTICIPANTS:Eighty-six kidney transplant recipients comprising 60 males and 26 females,aged 12-62 years old,who received first-time kidney transplantation,were included.The serum creatinine levels ranged between 65-267 μmol/L.METHODS:Peripheral blood of follow-up recipients was taken for anticoagulation using EDTA-Na2.Renal graft biopsy samples of some patients were collected.MAIN OUTCOME MEASURES:The expression rates of BAFF+,BAFF-R+,CD4+,CD8+,CD4+ CD25+ CD127-/low,CD134+,CD4+ CD 134+ and CD19+ BAFF-R+ in peripheral mononuclear cells were analyzed,and the ratio of CD4/CD8 was calculated.Biopsy tissue was subjected to pathological and immunohistochemical analyses.RESULTS:BAFF expression rate on the peripheral mononuclear cells was between 0.18%-76.97%.15%was used as the cut-off value.In the ≥15%group,the mean value of BAFF expression rate was 36.91%;BAFF+ mononuclear cells were not significantly correlated to the ratio of peripheral CD4+/CD8+ and the CD4+ CD25+ CD127-/low T lymphocytes.However,there were significant correlations between BAFF+ mononuclear cells and CD134+ lymphocytes or CD4+ CD134+ lymphocytes(P ＜0.01,P ＜0.05,respectively).While in the ＜15%group,there were no significant correlations among all indices.Pathological diagnosis confirmed that BAFF was expressed in the renal tubular epithelial cell cytoplasm and cytomembrane staining of some chronic rejection sections.CONCLUSION:Abnormal high expression of BAFF in peripheral mononuclear cells may be related to renal allograft rejection.
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Objective To observe the influence on early blood glucose by 3 L fluid replacementafter kidney transplantation. Methods Patients(60 cases) after kidney transplantation were randomly di-vidod into two groups.Group A used circular fluid replacement and Group B used 3L fluid replacement. Thelevel of blood glucose was detected before operation,after operation ,once every 8 hours at the first day,thenonce a day for the following six days. Results The level of blood glucose with 3 L fluid replacement waslower than that with circular fluid replacement,especially from the fast day to the fourth day after operation(P < 0.05). Conclusions The method with 3 L fluid replacement surpasses obviously circular fluid re-placement in blood glucose control after kidney transplantation.