PI3-K/PKB/NF-κB and p42/44 MAPK pathway mediates inhibition of lipoxin A_4 on CTGF-induced production of RANTES in mesangial cells

In order to investigate the regulatory role of connective tissue growth factor （CTGF） on production of RANTES （regulated on activation, normal T cell expressed and secreted） in rat glomerular mesangial cells, and the modulatory effect of lipoxin A4 （ LXA4 ） on action of CTGF, and to explore the mechanisms of action of CTGF and LXA4, cultured rat mesangial cells were treated with CTGF, with or without preincubation with LXA4. Expression of mRNA was analyzed by RT-PCR. Protein of RANTES in the supematants was determined by ELISA. Monocyte transmigration was assessed by in vitro chemotaxis assay. Expression of p42/44 mitogen-activated protein kinase （MAPK）, phosphoinositide 3-kinase （ PI3- K） and protein kinase B （PKB） was assessed by Western blotting. DNA-binding activity of nuclear factor-roB （NF-kB） was determined by electrophoretic mobility shift assay （EMSA）. To observe whether transfection of LXA4 receptor homologue gene （LRHg） into mesangial cells intensified these modulatory effects of LXA4, mesangial cells were transfected with pcDNA3.1/LRHG vector. The results showed that CTGF enhanced the mRNA expression and protein release of RANTES, and the expression of phospho （P）-p42/44 MAPK, P-PI3-K, P-PKB and NF-kB. P-p42/44 MAPK blockade inhibited the CTgF-induced expression of P-p42/44 MAPK and partially decreased the level of RANTES in supematants. P- PI3-K blockade downregulated the CTGF-stimulated expression of P-PI3-K, P-PKB and NF-kB, and partially decreased the release of RANTES. NF-kB blockade abrogated the CTGF-activated NF-kB and partially decreased the secretion of RANTES. LXA4 dose-dependently inhibited the CTGF-stimulated above action. Transfection of LRHG into mesangial cells intensified these inhibitory effects of LXA4 on CTGFinduced release of RANTES and expression of the P-p42/44 MAPK. In conclusion, LXA4 inhibits CTGFinduced production of RANTES via PI3-K/PKB/NF-kB and p42/44 MAPK-dependent signal pathway, which is mediated by LRHG in rat mesangial cells.

加权Coxeter群(_3,)的胞腔(英文)

仿射Coxeter群(_3,S)可以被看做仿射Coxeter群(D_4,S)在满足条件α(S)=S的某种群自同构α下的不动点集合,设是D_4的长度函数.本文明显地刻画了加权Coxeter群(_3,)的所有左胞腔.同时证明了:加权Coxeter群(D_4,)和(_3,)的所有左胞腔都是左连通的,所有双边胞腔都是双边连通的.

E_6型Weyl群中左胞腔的左连通性(英文)

首先通过计算机编程找出E_6型Weyl群左胞腔的所有极短元,利用这些极短元证明了E_6型Weyl群的所有左胞腔都是左连通的,从而证明了Lusztig关于左胞腔左连通性的一个猜想在E_6型Weyl群中是成立的.

Effect of high glucose, angiotensin Ⅱ and receptor antagonist Losartan on the expression of connective tissue growth factor in cultured mesangial cells

To observe the effect of high glucose, angiotensin Ⅱ (AngⅡ) and Losartan on the expression of connective tissue growth factor (CTGF) mRNA in cultured mesangial cells (MCs) Methods MCs of SD rats were isolated and cultured High glucose (30 mmol/L) and AngⅡ (10 -9 , 10 - 7 , and 10 -5 mol/L) were added to the medium for 72 hours to observe the influence on CTGF mRNA expression Losartan of 10 -5 mol/L and AngⅡ of 10 -5 mol/L were added to the medium to observe the effects of Losartan on CTGF mRNA expression stimulated by AngⅡ The expressions of CTGF mRNA were detected by reverse transcriptase polymerase chain reaction (RT-PCR) Results RT-PCR showed that high glucose and AngⅡ up-regulated the expression of CTGF mRNA, and AngⅡ stimulated the expression in a dose-dependent manner Expression of CTGF mRNA induced by AngⅡwas partially suppressed by 10 -5 mol/L Losartan (P<0 05) Conclusions High glucose and AngⅡ can enhance the expression of CTGF mRNA and thus be involved in the process of renal fibrosis Losartan can have a partial fibrogenesis-inhibiting effect, with implications for the treatment of renal fibrosis

Cholesterol metabolic enzyme Ggpps regulates epicardium development and ventricular wall architecture integrity in mice

During embryonic heart development,the progenitor cells in the epicardium would migrate and differentiate into noncardiomyocytes in myocardium and affect the integrity of ventricular wall,but the underlying mechanism has not been well studied.We have found that myocardium geranylgeranyl diphosphate synthase(Ggpps),a metabolic enzyme for cholesterol biosynthesis,is critical for cardiac cytoarchitecture remodelling during heart development.Here,we further reveal that epicardial Ggpps could also regulate ventricular wall architecture integrity.Epicardium-specific deletion of Ggpps before embryonic day 10.5(E10.5)is embryonic lethal,whereas after E13.5 is survival but with defects in the epicardium and ventricular wall structure.Ggpps deficiency in the epicardium enhances the proliferation of epicardial cells and disrupts cell‒cell contact,which makes epicardial cells easier to invade into ventricular wall.Thus,the fibroblast proliferation and coronary formation in myocardium were found enhanced that might disturb the coronary vasculature remodelling and ventricular wall integrity.These processes might be associated with the activation of YAP signalling,whose nuclear distribution is blocked by Ggpps deletion.In conclusion,our findings reveal a potential link between the cholesterol metabolism and heart epicardium and myocardium development in mammals,which might provide a new view of the cause for congenital heart diseases and potential therapeutic target in pathological cardiac conditions.