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Background: Oral squamous cell carcinoma (OSCC) is the most predominant type of oral cancer which has a poor prognosis, with 5-year survival rates less than 50%. Clinical characteristics such as tumor position, TNM classification and method of treat- ment, as well as histological grades have all been studied as OSCC prognostic factors but evaluating the genetic expression is the evolving trend in early diagnosis. Aim: To compare the gene expression of TGF-?-1, GSK3, Pi3 kinase in OSCC and normal tissue samples and to correlate the expression levels of these molecules with the pathological grading and survival in OSCC patients. Also to understand the role of GSK3 in Pi3 kinase pathway and TGF-? signaling pathway in OSCC progression thereby attempting targeted therapy in OSCC patients. Materials and Methods: 10 OSCC samples as well as normal healthy samples were collected and RNA isolation was done us- ing RNA easy kit from Qiagen (Valencia, CA), and thensubjected to cDNA synthesis using Human TGF-?1, Human GSK3? and Human Pi3 kinase primers. Real time PCR was performed using gene specific primers at 40 cycles. The results were retrieved, tabulated and analyzed. Results: The current research results revealed that there were up regulation of mRNA expression in GSK3, TGF ?-1 and Pi3 kinase in OSCC patients than in healthy individuals. On comparison, Pi3 kinase showed highest mRNA expression levels than GSK3 and TGF ?-1. Conclusion: The expression of GSK3 and its role in activation of Pi3 kinase pathway plays a crucial role in progression of oral cancer and targeting GSK3?could be a novel and targeted approach for treating OSCC.
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Increase in size and number of bronchial blood vessels as well as hyperaemia are factors that contribute to airway wall remodelling in patients with chronic airway diseases, such as asthma and chronic obstructive pulmonary diseases (COPD). Expression of transforming growth factor 1 (TGF-1), a multifunctional cytokine as well as vascular endothelial growth factor (VEGF), a key angiogenic molecule, has been shown in the inflammed airways in patients with chronic airway diseases. TGF-1 has been implicated in the regulation of extracellular matrix, leading to airway remodelling in patients with chronic airway diseases. However, the role of TGF-1 in regulating VEGF expression in patients with chronic airway diseases, as well as the underlying mechanisms are not yet well established. We investigated whether TGF-1 stimulates VEGF expression in vitro and hence could influence vascular remodelling. Cultured human airway smooth muscle cells (HASMC) were serum deprived for 60 h before incubation with 5ng/ml of TGF-1 for different time points. Control cells received serum-free culture medium. TGF‑1, treatment resulted in time dependent HASMC cell proliferation with maximal values for DNA biosynthesis at 24 h and cell number at 48 h. Northern blot analysis of VEGF mRNA expression showed increased levels in cells treated with TGF-1 for 4 to 8 h. TGF-1 also induced a time-dependent release of VEGF proteins in the conditioned medium after 48 h of treatment. Furthermore, the ability of HASMC-released VEGF proteins to induce human umbilical vein endothelial cells proliferation was inhibited by VEGF receptor antagonist, confirming that TGF-1 induced VEGF was biologically active. We conclude that TGF-1 in addition to an extracellular matrix regulator also could play a key role in bronchial angiogenesis and vascular remodelling via VEGF pathway in asthma.
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Objective:To investigate whether the expression of protein VEGF and TGF-?1 can be used as an indextoestimate injuryage in the field of forensic medicine by approaching the temporal relation of VEGF and TGF-?1 expression with injury in the healing process of the incised wounds on rat skin.Methods:Experimental rat models were established by incisions made on the rat skin.the rat models were divided randomly into three groups:the experimental group,the normal group,and the postmortem injured group.The expression of VEGF and TGF-?1 were observed with Immunohistochemical techniques in their process of cicatrization.Results:In the experimental group,the expression of VEGF and TGF-?1 were higher than those in the normal control and postmortem injury group(P
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Objective:To detect the expression of TGF-?1 in tibia and fibula fracture with two methods of compression plate fixation and intramedullary nail fixation,and to evaluate their therapeutic effects.Methods:117 patients with non severe tibia and fibula fractures were separated into two groups.One group received pressurized plates fixation for treatment,the other received intramedullary nail fixation.On 1,7,30 and 90 days after surgery,TGF-?1 was detected by ELISA,and on 30 days after surgery the clinical efficacy were also assessed. Results:The TGF-?1 content increased on 7 days as compared with that on 1 days after surgery,and the TGF-?1 content gradually decreased at on 30 to 90 days after surgery.The TGF-?1 content in compression plate fixation group were lower than that in intramedullary nailing group every points of four days(P
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[Objective] To study the mechanisms and effects of panax notoginsenosides(PNS)on myocardial fibrosis in chronic viral myocarditic(VMC)mice.[Methods]The model mice with VMC at chronic status were established by repetitive infection of Coxsckievirus B3m(CVB3m).Heart changes of myocardium and collagen hyperplasia were observed by HE and VG stain.Collagen volume fraction(CVF)and perivascular circuferential area(PVCA)were examined by pathological examination with computed processing.Myocardium TGF-?1 was detected by immunohistochemical method and mRNA expression of TGF-?1 was analyzed by Reverse transcription polymerase chain reaction(RT-PCR)method.[Results]Marked myocardial fibrosis was observed in chronic VMC model group.Compared with blank group,the index of CVF and PVCA was increased significantly(P
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Objective:To explore the effects of 1,25-dihydroxyvitamin D3 on renal expression of TGF-?1 and HGF in type 1 diabetic rats.Methods:30 Sprague-Dawley rats were randomized into 3 groups:normal control rats(group NC),diabetic rats(group DM ) and diabetic rats treated with 1,25-dihydroxyvitamin D3(group DC).Kidney-to-body weight ratio(KW/BW),mean glomerular volume(MGV),fractional mesangial area(FMA),urinary albumin excretion rate(UAER)and serum creatinine(Scr)were measured after 12 weeks of treatment,while transforming growth factor-betal(TGF-?1) expression in kidney cortex were observed by immunohistochemistry.The expression levels of TGF-?1 mRNA and HGF mRNA were detected by reverse transcription and polymerase chain reaction(RT-PCR) at the end of the experiment.Results:UAER,Scr,MGV,FMA and KW/BW ratio were significantly higher in the diabetic rats than those in the normal control rats(P
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Objective To investigate the effects of Thalidomide(THD)on transdifferentiation of human fetal lung fibroblast(HFL-F) to myofibroblast(MF) induced by Transforming Growth Factor-?1(TGF-?1) and the effects on trans differentiated MF.Methods HFL-F to MF trans-differentiation was induced with 5 ?g/L TGF-?1.The effect of 50 ?g/L THD on HFL-F to MF transdifferentiation was evaluated by measuring hydroxyproline(HYP) content with alkaline hydrolysis colorimetry,?-smooth muscle actin(?-SMA) protein with Western Blot,?-SMA and collagen Ⅲ(COL Ⅲ) mRNA with semiquantitative RT-PCR.Results THD inhibited TGF-?1 induced up-regulation of HYP and COLⅢ mRNA expressions(all P0.05).For HFL-F treated with 5 ?g/L TGF-?1 for 96 h,THD inhibited COLⅢ mRNA expression(P
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Objective: To determine the inhibitory effects of anti-bone sialoprotein(BSP) antibody on human breast cancer cells adhering to bone matrix in vitro.Methods: Expression of BSP in 3 different cancer cell lines(bone seeking breast cancer cell MDA-MB-231-BO,lung adenocarcinoma cell SPCA-1 and colon carcinoma cell LOVO)was detected immunohistochemically.Cells adhering test was carried out to investigate the adhering of the 3 different cancer cell lines to mouse bone matrix in vitro and the inhibitory effect of anti-BSP antibody on MDA-MB-231-BO cells adhering to mouse bone matrix;Enzyme-linked immunosorbent assay was carried out for quantitative detection of TGF-?.Results: BSP immunostaining was positive in MDA-MB-231-BO cells and negative in SPCA-1 and Lovo cells.The number of MDA-MB-231-F10 cells adhering to mouse bone matrix was significantly more than SPCA-1 or Lovo cells(P
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Objective To investigate the effect of high glucose on the expression of transforming growth factor-?1(TGF-?1),?-SMA,E-Cadherin in renal proximal tubular epithelial cells(HKCs)and role of AG490,an antagonist of Janus kinase.Methods Cultured HKCs cells were divided into four groups:low glucose group(LG),high glucose group(HG),high mannitol group(LG+M),and HG+AG490 group(AG).Immunoprecipitation and Western blot analysis were used to measure the expressions of tryosine phosphorylated Janus kinase 2(p-JAK2),STAT1,STAT3,p-STAT1,p-STAT3 and ?-SMA,E-Cadherin.The contents of TGF-?1 and type I collagen in the supernatants of the cultured HKCs were detected by ELISA.TGF-?1 mRNA were measured by RT-PCR.ResultsCompared with low glucose control group,the expressions of JAK2,p-STAT1,p-STAT3 and TGF-?1 mRNA were significantly increased in HG group from 6 to 72 h.Meanwhile,the contents of TGF-?1 and collagen I in the supernatants and the expression of ?-SMA were increased,the expression of E-Cadherin was decreased.The expression of JAK2,p-STAT1,p-STAT3 and TGF-?1 mRNA and the level of TGF-?1,collagen I in the supernatant s in HG+AG490 group were obviously lower than those of the HG group.The expression of ?-SMA and E-Cadherinwas also decreased in HG+AG490 group.Conclusion Activation of JAK/STAT signaling pathway seems to be involved in the high glucos induced overproduction of TGF-?1 and ECM proteins in HKCs.
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Objective To detect the effects of pancreatic kininogenase on the expression of TGF-?1 and collagen remodeling in myocardiom of spontaneously hypertensive rats(SHR).Methods Twenty-four male SHR(aged fifteen weeks)were randomly divided into three groups:SHR group,pancreatic kininogenase group and captopril group(n=8),8 male Wistar Kyoto rats with normol blood pressure was considered as control group.Pancreatic kininogenase was given by peritoneal injection(7.2 U? kg-1? d-1),captopril was given by intragastric administration(10 mg? kg-1? d-1),the rats in SHR group and control group were administered with 0.9% NaCl(2 mL ? kg-1? d-1)through peritoneal injection.After four-week experiment,the pressure was measured in rats througth carotid artery,the rats were sacrificed and left ventricular mass index,collagen volume fraction,peripheral vascular collagen area were measured.Myocardial tissue was stained with VG and pathological changes were observed.The expression of TGF-?1 were detected by immunohistochemical technique(SP method).Results The systolic blood pressure,left ventricular mass index,collagen volume fraction,peripheral vascular collagen area and the expression level of TGF-?1 in SHR group were obviously higher than those in control group(P0.05).Conclusion Pancreatic kininogenase can obviously control pressure and reverse myocardial fibrosis probably by decreasing the expression of TGF-?1 in SHR.
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Objective To investigate MVD, TSP-1, TGF-?1 expression in GH-Secreting Pituitary Adenomas by immunohistochemistry, and to correlate data with clinical characteristics.Methods The protein expression of TSP-1, TGF-?1 in 48 surgical specimens (21 invasive cases; 27 non-invasive cases) of pituitary adenomas was measured using immunohistochemical method. The relationship between the expression and clinical properties was examined. MVD was measured by detecting CD34.Results Compared with the noninvasive group, no difference of expression of CD34(t=2.257; P=0.083) was observed. The expression of TSP-1 in invasive group was low. The expression of TGF-?1 was higher in invasive cases than that in noninvasive ones. The expression of TGF-?1 had positive correlations with MVD; but there was no correlation between the expression of CD34 and the invasion of pituitary adenomas. In addition, MVD count was not associated with the expression of TSP-1. Size, sex or rate of recurrence did not influence MVD and TSP-1 expression. Conclusion MVD values do not necessarily represent angiogenesis in pituitary adenomas. TGF-?1 may increase MVD, and TSP-1 does not affect MVD in pituitary adenomas and angiogenesis may be regulated by other pathway.
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Objective To investigate the effect of pancreatic kininogenase on the expression of matrix metalloproteinases-2 2(MMP-2), transfer growth factor-?_ 1 (TGF-?_ 1 ) and ventriculer remodeling in spontaneously hypertensive rats (SHR). Methods Twenty-four male 15 weeks SHR were randomly divided into three groups: SHR group, pancreatic kininogenase treatment group(PK: 7.2 U/kg?d), captopril treatment group(Cap: 10 mg/kg?d)(n=8 in each), 8 Wister Kyoto were served as control. After four weeks, blood pressure were measured througth carotid artery catherization. Myocardial tissue was stained with VG and pathological changes were studied. MMP-2, TGF-?_ 1 were determined by immunohisto-chemical technique(SP method). Results In pancreatic kininogenase treated SHR, SBP(183?12 vs SHR: 234?23)mm Hg, LVMI(2.89?0.15 vs SHR: 3.06?0.18)mg/g, CVF(0.17?0.03 vs SHR: 0.26?0.05)%, PVCA(0.57?0.26 vs SHR: 0.99?0.47)% and expression of MMP-2, TGF-?_ 1 in SHR were significantly improved (P
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Objective To investigate the molecular mechanism of CCl_(4) inducing fibrosis in hepatic stellate cells.Methods The expression of Transforming growth factor-?1(TGF-?1) at mRNA and protein level were detected by RT-PCR method and Western blot analysis.The proliferation and cell cycle distribution were detected with MTT method and flow cytometry.Results After treatment by(10 mmol/L) CCL_(4) for 24 hours,the mRNA and protein expression of TGF-?1 in CCl_(4) group sharply increased.In the meantime,the proliferation of CCl_(4) group cells was markedly increased.There were less G_(0)/G_(1) phase_() cells and more G_(2)/M phase cells in CCl_(4) group than those in control group.Conclusion Suitable CCl_(4) may increase the expression of TGF-?1 and the proliferation of hepatic stellate cells,which is one of mechanisms leading to hepatic fibrosis.
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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
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[Objective]To demonstrate mechanism of ESW in curing osteogetic disorders,we studied expression of some osteogenetic factors in human mesenchymal stem cells(hMSCs)when exposed to ESW.[Method]After success in marrow aspiration,isolation and obtainment optimal experimental energy,a dose of 5kV and 100 times of ESW was applied to hMSCs of passage 1.The expression of IGF-Ⅰ and TGF-?1 were examined by immunocytochemical staining.[Result]The cytochemical staining results showed that expression of IGF-Ⅰ and TGF-?1 appeared at different passage of hMSCs after ESW intervention.Appearance of IGF-Ⅰ was earlier than TGF-?1 which didnt express until passage 7.At the same interval,the expression of IGF-Ⅰ and TGF-?1 in control group difference is lower than ESW group,respectively(P
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[Objective]To evaluate whether transplanted marrow mesenchymal stem cells interfered in TGF-?1 can differentiate to nucleus pulposus cells and increase the amount of proteoglycan and collagenase Ⅱ content in intervertebral discs.[Method]We used an in vivo model to investigate the feasibility of marrow mesenchymal stem cells that cultured in vitro and interfered in TGF-?1 delivery,retention,and survival in the degeneratived disc space.In 2,4,6,8 weeks we used immunohistochemical staining to determine the change of collagenase Ⅱ content;spectrophotometry to determine the change of amount of proteoglycan with Phlorglucinol;the experiment date were analyzed by SPSS 11.5 soft ware.[Result]We found MSCs could maintain viability and proliferate within the rabbit inter vertebral disc.The amount of proteoglycan and collagen Type Ⅱ content of the intervertebral in matrix synthesis in the experiment group was increased in 8 weeks.We found no changes in the modle group.[Conclusion]Our data suggest that transplanted marrow mesenchymal stem cells in vivo can survive and increase proteoglycan and collagen Type Ⅱ amount interfered in TGF-?1 in some periods,which support its potential use as a treatment of intervertebral disc degeneration.
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T polymorphism of TGF-?1 gene related with the degree of L_(4?5) and L_5S_1 disc degeneration.
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[Objective]To study the effect of TGF?1 on the expression of fibronectin and ?1 integrin receptor in chronic viral myocarditis of myocardial fibrosis induced by repeated virus infection and the interventional effect of QingXin.[Methods] Establish mice model of myocardial fibrosis in chronic stage of viralmyocarditis,then divide the mice model into model group,captopril group,QingXinⅡ high dose,medium dose and low dose groups.The normal group and model group are given saline through stomach perfusing,as well as the treated group are given respectively captopril and QingXinⅡ high,medium and low dose in the same way.After the treatment,hearts are collected,CVB3-RNA are detected by RT-PCR,TGF?1 and FN are detected by immunohistochemical technique,integrin?1 are analyzed by immunofluorescence staining-confocal laser scanning.[Results] After having done the model,TGF?1,integrin?1,FN has increased obviously;virus can be detected in themyocardium by RT-PCR;after the intervention of QingXinⅡ,TGF?1,integrin?1,FN has decreased,virus has reduced in treated group.[Conclusion] Virus,TGF?1,integrin?1 and FN have important effects on the formation ofmyocardial fibrosis;QingXinⅡ has the function of antivirus and anti-myocardial fibrosis.
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Objective To study the relationship between the changing law of cytokine gene expression profile and tumor-related fatigue and to verify the preliminary theory conclusion that the pathogenesis of tumor-related fatigue may be due to the up-regulation of the TNF,TGF-?,etc.Methods The changing characteristics of gene expression profile of cytokines were studied in peripheral blood mononuclear cells samples with gene chip.Results The gene expression level of TNF-? and TGF-?1 was up regulated.Conclusions The experimental results conform to the theory research conclusion and show that the pathogenesis of tumor-related fatigue due to the up-regulation of the gene expression level of TNF and TGF-?.
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Objective To investigate the protective effect and possible mechanism of Decorin on pulmonary fibrosis.Methods A total of 90 healthy Wistar rats were randomly divided into three groups:group A served as control group,group B was injected BLMA5 through trachea,group C was injected BLMA5 and received treatment of Decorin.Ten rats in each group were killed 7、14、28 days after intratrachael instillation.TGF-?_1 expression was measured by immunohistochemical technique.The degree of alveolitis and fibrosis were measured by HE staining.The contents of hydroxideproline were measured in the homodenate of the rat lung.Results The expressions of TGF-?_1 were increased gradually in group B;in group C the expressions were decreased significantly than group B(P