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OBJECTIVES: Here, we aimed to compare the clinical effects of mycophenolate mofetil combined with either tacrolimus or with cyclophosphamide on lupus nephritis (LN) and to analyze their influence on the expression of cystatin C and on transforming growth factor-1 (TGF-β1). METHODS: A total of 234 patients were randomly divided into two groups: group A, for mycophenolate mofetil combined with tacrolimus (n=117) and group B, for mycophenolate mofetil combined with cyclophosphamide (n=117). The enzyme-linked immunosorbent assay was adopted to detect the expression levels of serum TGF-β1 and cystatin C before and after treatment. RESULTS: The total effectiveness rate in group A was much higher than that in group B. The times of effectiveness and effect validity in group A were much lower than those in group B. The expression levels of serum TGF-β1 and cystatin C decreased slightly after treatment in the two groups, and those of group A were much lower than those of group B. CONCLUSIONS: The combination of mycophenolate mofetil and tacrolimus showed better clinical efficacy on LN and was safer than that of mycophenolate mofetil and cyclophosphamide. Moreover, the drug combination of mycophenolate mofetil and tacrolimus greatly reduced the expression levels of serum TGF-β1 and cystatin C.
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Humans , Lupus Nephritis/drug therapy , Mycophenolic Acid/therapeutic use , Tacrolimus/therapeutic use , Cyclophosphamide/therapeutic use , Drug Therapy, Combination , Immunosuppressive Agents/therapeutic useABSTRACT
Objective: To investigate the effect of bromodomain-containing protein 4 (BRD4) gene on the apoptosis of cardiomy
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Objective:To examine the expression of transforming growth factor I(TGF-β1) and bone morphogenetic protein-9 (BMP-9) in human nonunion tissues,and to evaluate the clinical significance.Methods:The number of hypertrophic nonunion tissue samples and atrophic nonunion tissue samples were collected from Department of Orthopedics,the Second Xiangya Hospital of Central South University and Suzhou Kowloon Hospital Affiliated to School of Medicine of Shanghai Jiao Tong University between 2010 and 2014.Semi-quantification of SP immunohistochemical method and pathological image analysis software IPP6.0 were used to analyze the expression of TGF-β1 and BMP-9.Nonunion type,patients' age and nonunion time were statistical analyzed.Results:The absorbance values of TGF-β1 and BMP-9 in the hypertrophic nonunion tissues were 0.3236±0.0390 and 0.1337±0.0400,respectively;while the absorbance values of TGF-β1 and BMP-9 in the atrophic nonunion tissues were 0.3191±0.0369 and 0.1373±0.0423,respectively,with no significant difference between the two types of tissues (both P＞0.05).There was also no significant difference in patients' age and bone nonunion time between them (all P＞0.05).Conclusion:There is no significant difference in osteogenic potential between the hypertrophic nonunion tissues and the atrophic nonunion tissues.
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OBJECTIVE: To observe the intervention effect of polyguanylic acid( Poly G) on silicosis fibrosis in rats and to explore its possible mechanism. METHODS: Specific pathogen free adult male SD rats were randomly divided into 6 groups:control group,silicosis model group and 4 intervention groups( intervention group 1,2,3 and 4),with 5 rats in each group. Except for the control group,the other 5 groups were treated with 1. 0 m L silica suspension( 50. 0 g / L mass concentration) by intratracheal intubation,four intervention group was given by intraperitoneal injection of 1,2,3 and 4doses of Poly G at 2. 5 mg / kg body weight after establishing the model for 1 to 21 days. All rats were sacrificed 28 days after silicosis model establishment. Lung pathological changes were observed and the pulmonary fibrosis was evaluated by Ashcroft scores. The expression of Macrophage receptor with collagenous structure( MARCO),transforming growth factor-β1( TGF-β1),E-cadherin,Vimentin and α-smooth muscle actin( α-SMA) protein were detected by western blot.RESULTS: In the model group,a large number of dust cell aggregates were found in the alveolar cavity and diffuse collagen deposition appeared in the pulmonary interstitial,indicating that silicosis model was successfully constructed. The alveolar structure of the single dose intervention group was integral and the degree of fibrosis was significantly less than that of the silicosis model group. Compared with the control group,MARCO,TGF-β1,Vimentin and α-SMA expression levels of silicosis model group were increased,the expression level of E-cadherin decreased, the difference was statistically significant( P < 0. 05). Compared with the silicosis model group,TGF-β1,Vimentin and α-SMA expression levels of single dose intervention group decreased,E-cadherin expression level increased,the difference was statistically significant( P < 0. 05). The dose-response relationship could not perceived between the Poly G intervention times and the Ashcroft scores or the protein expression levels of MARCO,TGF-β1,E-cadherin,Vimentin and α-SMA respectively. CONCLUSION: Poly G can effectively reduce lung inflammation and fibrosis in rats. The effect of single dose intervention( 2. 5 mg / kg body weight,intraperitoneal injection) at the first day after silica exposure is the best. The mechanism of action may be related to the low-does Ply G which can inhibit the epithelial-mesenchymal transition and then result in the decrease of collagen synthesis.
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Thrombospondin-1 (THBS-1),a kind of extracellular matrix proteins,whose biological action played an important role in corneal wound healing has became a research highlight.The currently research findings showed that THBS-1 could promote the healing of epithelium,stroma and endothelium through activating the transforming growth factor-β1 (TGF-β1) which can accelerate cell proliferation,promote stroma forming and inducing cell migration.It is worthful in clinical treatment of all kinds of corneal wound healing.Now we summarized the research developments which have been acquired in the field recently in this article.
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OBJECTIVES: The aim of this cross-sectional study was to evaluate whether interleukin 10 (IL10) and transforming growth factor β1 (TGFβ1) gene polymorphisms were associated with persistent IgE-mediated cow's milk allergy in 50 Brazilian children. The diagnostic criteria were anaphylaxis triggered by cow's milk or a positive double-blind, placebo-controlled food challenge. Tolerance was defined as the absence of a clinical response to a double-blind, placebo-controlled food challenge or cow's milk exposure. METHOD: The genomic DNA of the 50 patients and 224 healthy controls (HCs) was used to investigate five IL10 gene polymorphisms (-3575A/T, -2849A/G, -2763A/C, -1082G/A, -592C/A) and one TGFβ1 polymorphism (-509C/T). RESULTS: Among the five IL10 polymorphisms analyzed, homozygosis for the G allele at the -1082 position was significantly higher in the patients compared with the healthy controls (p = 0.027) and in the persistent cow's milk allergy group compared with the healthy controls (p = 0.001). CONCLUSIONS: Homozygosis for the G allele at the IL10 -1082G/A polymorphism is associated with the persistent form of cow's milk allergy. .
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Child , Female , Humans , Male , Immunoglobulin E/immunology , /genetics , Milk Hypersensitivity/genetics , Polymorphism, Genetic/genetics , Polymorphism, Single Nucleotide/genetics , Transforming Growth Factor beta1/genetics , Brazil , Case-Control Studies , Cross-Sectional Studies , Gene Frequency , Logistic Models , Milk Hypersensitivity/immunology , Polymerase Chain Reaction , Risk FactorsABSTRACT
Several studies have shown that hepatocyte growth factor (HGF) ameliorates renal interstitial fibrosis, but the mechanism is not fully clear. This study was designed to examine whether HGF can relieve renal interstitial injury in 5/6 nephrectomized rats, and to confirm whether this function was associated with decrease in -smooth muscle actin (-SMA) and transforming growth factor-beta1 (TGF-1) expression. The animals were randomized into 8 groups comprising 6 animals (n = 6) each: control (group I), PCI-neo (group II, 900 μg), sham-operation (group III，not nephrectomy), model or 5/6 nephrectomy group (group IV), lotensin group (an angiotensin converting enzyme inhibitor, group V, 0.6 mg/100 g/day for 5 weeks), low-dose PCI-neo-HGF group (group VI, 690 μg), high-dose PCI-neo-HGF group (group VII, 1380 μg) and lotensin + high-dose PCI-neo-HGF group (group VIII, 0.6 mg/100 g/day for 5 weeks, 1380 μg). The animals were sacrificed in the 5th week after 5/6 nephrectomy. The specimens of kidneys were used for pathological examination (hematoxylin-eosin staining), detection of -SMA and TGF-1 mRNA (Reverse transcriptase-polymerase chain reaction) and protein (Western blot and immunohistochemistry) expression. The results showed that in 5/6 nephrectomized rats blood urea nitrogen (BUN), serum creatinine (CRE) and 24 h urinary albumin excretion (UAE) were increased, renal interstitium was injured seriously and -SMA, TGF-1 mRNA and protein expression were elevated compared with those of control. The above changes were ameliorated and -SMA and TGF-1 expression was reduced by both PCI-neo-HGF and lotensin. The lotensin + high-dose PCI-neo-HGF group rats exhibited the most significant therapeutic effect both in decreasing the BUN, CRE and 24 h UAE and in relieving renal interstitial injury. In conclusion, the study demonstrated that HGF can relieve renal interstitial injury and this protection was associated with down-regulation of –SMA and TGF-1 expressions.
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0.05). Levels of TGF-?1 and PDGF in microparticle platelet frozen powder were higher than those in fresh platelet(P
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Objective:To investigate the effect of Shuxuetong injection on the urine protein excretion changes and expressions of transforming growth factor ?(1TGF-?1)and collegen type Ⅳ(Col-Ⅳ)in renal tissues in diabetic rats.Methods:Diabetic nephropathy was induced by intraperitoneal injection of streptozotocin(STZ).Rats were randomly divided into control group,untreated DN group,Shuxuetong group and Benazepril group.Urinary albumin excretion rate(UAER),?2-microglobulin(?2-MA)and KW/BW(kidney weight/body weigh)were determined 8 weeks later.The expressions of TGF-?1 and Col-Ⅳ in renal tissues were determined by using immunohistochemical methods.Results:After interference,compared with the untreated DN group,UAER,?2-MA,KW/BW in the Shuxuetong group were significantly down-regulated(P
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OBJECTIVE:To investigate the effect of extract of Ginkgo biloba(EGb) on levels of Endothelin-1(ET-1) and transforming growth factor ?1(TGF-?1) in renal tissue of diabetic rats.METHODS:Twenty-four male Sprague-Dawley rats were randomly divided into three groups:normal control group,diabetic model group and EGb-treated group.The levels of blood glucose,insulin,total cholesterol(TC),total triglycerides(TG),creatinine clearance(Ccr),urinary albumin excretion(UAE),and urinary ?2-MG were measured after 8-week corresponding treatment.Expression of SET-1,UET-1,and RET-1 was examined by radioimmunoassay technique.Expression of STGF-?1 and UTGF-?1 in serum and urine was examined by enzyme linked immunosorbent assay(ELISA).RESULTS:The concentrations of blood glucose,blood insulin,TC and TG increased significantly in diabetic group,which were down-regulated by EGb.Levels of ET-1 and TGF-?1.in both blood and urine and the ET-1 level in renal tissues were significantly higher in diabetic model group than in normal control group(P
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Objective To investigate the effect of chymase on the proliferation of rat cardiac fibroblasts (CFs) and the role of transforming growth factor-?1 (TGF-?_1).Methods Cultured CFs of neonatal SD rats were isolated by trypsinization.Cell number and DNA synthesis were evaluated by MTT assay (A_(490) value) and [~3H]-deoxythy- midine [~3H]-TdR incorporation.The mRNA expression of TGF-?_1 in CFs was determined by RT-PCR.Results Chymase increased CFs numbers and [~3H]-TdR incorporation in a dose-dependent manner.The A_(490) value of CFs stimulated by 15,30 and 60 ng/mL chymase was 0.263?0.033,0.348?0.031 and 0.387?0.026,respectively, which were all significantly higher than that of control (0.201?0.019,P
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Objective To explore the possible mechanism and protective effect of Xuebijing injection (血必净注射液)and dexamethasone on rats with paraquat-induced chronic pulmonary injury.Methods Thirty male Wistar rats were randomly divided into six groups:normal group(n=5),model group(n=5), treatment groups(n=20).In the normal group,normal saline was used,while in the other groups,20% paraquat 80 mg/kg was injected peritoneally for poisoning.After 2 hours of intoxication,low dose Xuebijing injection(1.25 g/kg),high dose Xuebijing injection(2.50 g/kg),dexamethasone(25 mg/kg),high dose Xuebijing injection combined with dexamethasone(combined group)respectively were administered into the four different treatment groups,equal amount of normal saline was given to the normal and model groups,and the treatment continued for 4 days.At 28 days after paraquat injection,5 rats in each group were killed respectively,serum transforming growth factor-?1(TGF-?1)and hydroxyproline(HYP)level in the lung homogenate were measured,and pulmonary coefficient and histological changes were observed.Results In the treatment groups,the levels of serum TGF-?1 and lung tissue HYP,pulmonary coefficient were leas than those of model group,and among the treatment groups,combined group had the best results(all P
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Objective To investigate the biological effect of transforming growth factor-?1(TGF-?1) on inducing myofibroblast formation in hypoxic pulmonary vascular remodeling.Methods Forty male Wistar rats were exposed to hypoxia for 0,3,7,14 or 21 days.Mean pulmonary arterial pressure(mPAP),vessel morphometry,right ventricle hypertrophy index(RVHI) were measured.Immunocytochemistry was used to measure the expression of ?-Smooth-muscle actin(?-SMA) and TGF-?1 in pulmonary artery walls and in situ hybridization was used to measure the expression of TGF-?1 mRNA in pulmonary artery walls.Ultrastructure alveolar wall vessels were observed by electron microscopy.Human embryonic lung fibroblasts(KMB17) phenotype after induction of hypoxiaand TGF-?1 were recorded through cell culture.Results(1) mPAP increased significantly after 7-day of hypoxia(P
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Objective To investigate the expression of extracellular signal-regulated kinase 1/2(ERK1/2) and transforming growth factor ?1(TGF-?1) in heart of spontaneous hypertensive rat.Methods The expression of ERK1/2 and TGF-?1 was determined by immunohistochemistry and Western blot.Results In arteriole of the heart of 8,16,and 20 week-old SHR,the rate of positive ERK1/2 staining at the endothelium(15.38%,76.97% and 72.72%,respectively) and at the vascular smooth muscle cell(VSMC) of 16 and 20 week-old SHR(5.49% and 6.83%,respectively)were significantly higher than that of control group(P
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Objective To observe the effect of Vascular Endothelial Growth Factor(VEGF) to the expression in hepatoma cells affected by TGF-?1 and hopxia. Methods HepG2 cells were cultured in vitro, and treated with different doses of TGF-?1 and Cobalt chloride hexahydrate(CoCl2), or with TGF-?1 and CoCl2. The change of VEGF protein and mRNA was detected by immunohistochemistry and semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Results Immunohistochemistry and RT-PCR showed that the expression of VEGF protein and mRNA were significantly higher in TGF-?1 groups or CoCl2 groups than that of control group(P
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Objective To investigate the impact of ovarian carcinoma cells on the expression of vascular endothelial growth factor(VEGF) in human peritoneal mesothelial cells(HPMC). Methods HPMC was incubated with ovarian carcinoma cell line in SKOV3 conditioned medium(SKOV3-CM) for(3～ 72 hrs ). RT-PCR was used to detect VEGF gene expression. VEGF protein expression in cell lysates was assessed by ELISA. HPMC was cultured for 24 hrs in SKOV3-CM or SKOV3-CM with anti-transforming growth factor?1(TGF-?1)neutralizing antibody,and the changes in VEGF gene and protein expression were examined. Results VEGF mRNA and protein were detected in HPMC without stimulation of SKOV3-CM. SKOV3-CM significantly induced HPMC VEGF mRNA and protein expression in a time-dependent manner and the induction started 6h(for mRNA) and 12 h (for protein) after the treatment(P
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Objective To investigate the renoprotective effect of reduced glutathione on streptozotocin-induced diabetic rats and its possible mechanism.Methods Streptozotocin-induced diabetic rats received aminoguanidine(50 mg?kg~(-1)?d~(-1)) and reduced glutathione 400 mg?kg~(-1)?d~(-1) intraperitoneally respectively or synchronously for(8 weeks.) The expression of TGF-?1 mRNA and protein in renal cortex were determined by reverse transcription polymerase chain reaction(RT-PCR) and immunohistochemistry respectively.The mean glomerular area(MGA) and volume(MGV) were measured by image analysis system.The changes of creatinine clearance rate(Ccr),the kidney weight/body weight ratio and the urinary albumin excretion rate(UAER) were determined.Results By the end of 8 weeks,the Ccr,UAER,MGA,MGV,kidney weight/body weight ratio,the contents of TGF-?1 mRNA in renal cortex were increased significantly in DM groups compared with the blank control group(P
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0.05).The level of TGF-?1 in lung homogenate of model group was higher than blank group and Danshen group(P0.05).Conclusion TGF-?1 participates in invasion process of COPD and Danshen injection can interve COPD airway remodeling by down-regulating the level of TGF-?1.
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[Objective] To study the methods of inducing bone mesenchymal stem cells(BMSCs)of rabbits into chondrocytes in vitro and the interaction of transforming growth factor ?1(TGF-?1),insulin-like growth factor-Ⅰ(IGF-Ⅰ)and basic fibroblast growth factor(bFGF).[Methods]BMSCs of rabbits were primarily cultured and subcultured in vitro,and then divided into four groups according to the difference of factors:group A receiving TGF-?1 and bFGF;group B receiving TGF-?1 and IGF-Ⅰ;group C receiving TGF-?1;group D receiving no cell growth factor.After three weeks all the four groups were detected by methyl thiazolyl tetrazolium(MTT)assay,measurement of glycosaminoglycan(GAG)and immunohistochemistry.[Results]Immunohistochemical detection of collagen Ⅱ was positive in groups A,B and C.The results of the MTT assay and the GAG content in groups A and B were obviously higher than those in groups C and D.[Conclusion]Rabbit BMSCs can be induced into chondrocytes under certain conditions.TGF-?1,IGF-Ⅰ and bFGF have synergy effect in the differentiation from BMSCs into chondrocytes.
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[Objective]To induce TGF-?1 gene which can increase ECM synthesis into adipose tissue derived stem cells(ADSCs) by employing gene transfer techniques and observe whether TGF-?1 gene could expresse continuously and whether type II collagen and aggrecan are synthesized in order to provide experimental data for constructing tissue-engineering cartilage. [Method]ADSCs were transferred with TGF-?1 gene ,TGF-?1,FN,ColⅡ and aggrecan were detected with RT-PCR and TGF-?1 protein was detected with Western-blot.[Result]RT-PCR demonstrated that the expression of TGF-?1,FN,ColⅡ and aggrecan in the TGF-?1 gene transferred groups increased more evidently than non-gene groups and control groups (P