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Objective To investigate the effect of histone acetylation change on the transforming growth factor β1 (TGF-β 1)-associated plasminogen activator inhibitor 1 (PAI-1) regulation in mesangial cells (MCs).Methods MCs were transfected with histone acetyltransferase (HAT)CREB-binding protein(CBP),P300 or histone deacetylase (HDAC) 1,3,5 expression vectors,followed by luciferase assay,real-time PCR and Western blotting to see the change of PAI-1 gene's transcriptional activity,mRNA and protein in response to TGF-β1.HDAC inhibitor trichostatin A(TSA)was used and TGF-β1-Smad signaling activity was detected also in this experiment.Results TGF-β1 enhanced PAI-1 transcriptional activity and mRNA expression (P ＜ 0.05).Over-expression of CBP or P300 significantly increased TGF-β1-associated PAI-1 transcriptional activity,mRNA and protein expression (P ＜ 0.05).On the contrary,over-expression of HDAC1,3,5 or dominant negative CBP or dominant negative P300 obviously reduced PAI-1 gene's expression induced by TGF-β1 (P ＜ 0.05).Change of HAT/HDAC did not affect TGF-β1-associated Smad2/3 phosphorylation.TSA enhanced TGF -β1 induced PAI-1 gene's regulation markedly,but did not change TGF-β1-Smad2/3 signaling activity.Conclusion Change of histone acetylation can affect TGF-β1 associated PAI-1 gene's regulation in MCs.
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Objective To observe therapeutic effect and safety of tacrolimus on idiopathic membranous nephropathy(IMN)with nephrotic syndrome in different courses of treatment.Methods Twenty patients with nephritic syndrome caused by idiopathic membranous nephropathy were divided into short-term(10 cases)and long-term(10 cases)groups randomly.Short-term group and long-term group were treated with tacrolimus and prednisone for 6 months and 24 months repectively,then obersve treatment effect,concentration changes of tacrolimus,recurrence and side effects in 2 groups.Results Five patients obtained complete remission after 6 months of treatment in the short-term group;4 patients obtained partial remission;1 patient had no response.Average concentration of tacrolimus remained 5～7 ?g/L in the period of treatment,and 6 cases recurred.Six patients obtained complete remission and 3 patients obtained partial remission after 24 months of treatment in the long-term group;1 patient had no response.Concentration of tacrolimus in the long-term group remained same as the short-term group at 5～8 ?g/L at 6 months,3.38～4.36 ?g/L at 12 months;no case recurred after treatment,the rate of which was significantly lower than the short-term group.Conclusion Short-term and long-term treatment of tacrolimus can relieve IMN evidently;low concentration of tacrolimus in the long-term group can alleviate the state of illness persistently with low recurrence rate.
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Objective:To observe the theraputic effect and changes of glomerular extracellular matrix components(ECM) and PAI-1 and their relationships after cure with methyl-prednisone on immune complexes nephritis rats.Methods:Immune complexes nephritis rats model were induced with C-BSA.Levels of FN,LN in different treatment groups were analyzed by ELISA, level of PAI-1 in rats renal tissue was determined by color developing substrate,was theraputic effect of methyl-prednisone with 24 hours volumes of urine protein.Results:The levels of PAI-1,FN and LN of model groups were significantly higher than those of normal and control groups,and PAI-1 was significantly correlated with LN and FN,Glomerular mesangial matrix proliferated slightly and moderately;The levels of FN,LN and PAI-1 decreased signifcantly and glomerular mesangial matrix proliferation lessen differently after cure of methyl-prednisone for 1 and 2 weeks,but not reaching the level of normal groups;24 hours volumes of urine protein decrease significantly in treatment groups.Conclusion:The ECM accumulation correlate with PAI-1 increase in immune complexes rats,methyl-prednisone may affect ECM accumulation by interfering with PA/PAI-1 system to reach a treatment purpose.
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Objective:To investigate the effect of methylprednisolone that decrease plasminogen activator inhibitor-1(PAI-1) in plasma through mediating the PA/plasmin system.Methods:Employed immunohistochemical technique-ELISA to determine PAI-1 level in plasma.Results:①PAI-1 in LN patients is significantly higher than that in the control group (P0.05).Conclusion:It is thus proved that methylprednisolone is capable of decreasing PAI-1 in plasma through mediating the PA/plasmin system and two shocks is the minimum for effective cure. [