Idiopathic pulmonary fibrosis in relation to gene polymorphisms of transforming growth factor-β1 and plasminogen activator inhibitor 1

Background Idiopathic pulmonary fibrosis （IPF） is a progressive and lethal fibrotic lung disease of unknown etiology. Host susceptibility or genetic factors may be important for the predisposition to it. Transforming growth factor-β1 （TGF-β1 a potent profibrotic cytokine） and plasminogen activator inhibitor 1 （PAl-1） play important roles in the development of pulmonary fibrosis. The objective of the study was to investigate the association between the gene polymorphisms of TGF-β1 869 T〉C and PAl-1 4G/5G and the susceptibility to IPF in Han ethnicity. Methods Polymerase chain reaction （PCR） and restriction fragment length polymorphism were performed to analyse the gene polymorphisms of TGF-β1 in 869T〉C and PAl-1 4G/5G in 85 IPF patients and 85 healthy controls matched in age, gender, race and smoker status. Results There was a significant difference in 869T〉C genotype distribution of TGF-β1 between IPF cases and controls, a significant negative association between TC genotype and the development of IPF （OR=0.508, 95% CI： 0.275-0.941） and a positive association between CC genotype and the development of IPF （OR=1.967, 95% CI： 1.063-3.641）. There was a significant positive association between PAl-1 5G/5G genotype and the development of IPF （OR=0.418, 95% CI： 0.193-0.904）. Conclusions Gene polymorphisms of TGF-β1 in 869T〉Cand PAl-1 4G/5G may affect the susceptibility to IPF in Han ethnicity. Further investigations are needed to confirm these findings and assess their biological significance in the development of the disease in this ethnic population.

Effect of cytokine gene polymorphism on histological activity index, viral load and response to treatment in patients with chronic hepatitis C genotype 3

AIM： To investigate the association between cytokine gene polymorphism and disease status in chronic hepatitis C genotype 3 by liver biopsy, ALl, HCV RNA levels and response to treatment. METHODS： Patients with chronic hepatitis C genotype 3 were analyzed for single nucleotide polymorphisms of interleukin （IL）-10, IL-1 beta, interferon-gamma （IFN-y）, tumor necrosis factor-alpha （TNF-y） and transforming growth factor-beta （TGF-β） by polymerase chain reaction using sequence-specific oligonucleotide primers. Liver biopsies were assessed by modified histological activity index （HAI） scoring system using a scale of 0-18 for grading the necro-inflammatory activity and 0-6 for staging the fibrosis. HCV RNA levels were determined by bDNA assay. The patients were treated with interferon alpha and ribavirin for 6 mo. Sustained virological response was assessed 6 mo after the completion of the treatment. RESULTS： Out of the 40 patients analyzed, 26 were males. Mean age was 40.5±12.5 years （range 18- 65 years）. The frequencies of different dimorphic polymorphisms based on single nucleotide substitution were as follows： IL-10-1082 G/A 85%, A/A 12.5%, G/ G 2.5%; IL-10-819 A/C 87.5%, C/C 10%, A/A 2.5%; IL-10-592 C/A 72.5%, C/C 27.5%; IL-1 C 90%, U 10%; IFN-874 T/A 50%, T/T 27.5%, A/A 22.5%; TNF-308 A/G 95%, G/G 5%; TGF-10 T/C 52.5%, C/C 35%, T/T 12.5%. The mean grades of necroinflammatory activity of different genotypes of IL-10 at promoter site -1082 were A/A = 3.6, A/G = 5.0, and G/G = 10.0 and the difference was significant （P = 0.029）. The difference in the stage of disease at a scale of 0-6 was A/A 0.8, A/G 2.3, and G/G 4.0 （P = 0.079）. The difference in the HAI seemed to be related to the presence of allele -1082G.For IL-10 -819 genotypes, mean scores of fibrosis were A/A = 6.0, A/C = 2.2, and C/C = 1.0 （P = 0.020） though the inflammatory activity was not much different. No significant differences in HAI were noted among polymorphisms of other cytokines. Moreover, ALT and HCV RNA levels were not significantly different among different cytokine polymorphisms. There was a significant correlation of HAI and HCV RNA levels with the duration of disease. TGFI3 -10 genotype CC patients had a better end of treatment response than those with other genotypes （P = 0：020）. Sustained virological response to the treatment was not influenced by the cytokine polymorphism. No effect of other factors like viral load, degree of fibrosis, gender, steatosis, was observed on sustained virological response in this population infected with genotype 3. CONCLUSION： There is no significant correlation between cytokine polymorphisms and HAI except for the polymorphisms of anti-inflammatory cytokine IL-10, which may influence hepatic inflammatory activity and fibrosis in patients with chronic hepatitis C genotype 3. Sustained virological response in this genotype does not seem to be influenced by cytokine gene polymorphisms.

Molecular Tissue Engineering: Applications for Modulation of Mesenchymal Stem Cells Proliferation by Transforming Growth Factor β_1 Gene Transfer

The effect of transforming growth factor β 1 (TGF β 1 ) gene transfection on the proliferation of bone marrow derived mesenchymal stem cells (MSC S ) and the mechanism was investigated to provide basis for accelerating articular cartilage repairing using molecular tissue engineering technology. TGF β 1 gene at different doses was transduced into the rat bone marrow derived MSCs to examine the effects of TGF β 1 gene transfection on MSCs DNA synthesis, cell cycle kinetics and the expression of proliferating cell nuclear antigen (PCNA). The results showed that 3 μl lipofectamine mediated 1 μg TGF β 1 gene transfection could effectively promote the proliferation of MSCs best; Under this condition (DNA/Lipofectamine=1μg/3μl), flow cytometry and immunohistochemical analyses revealed a significant increase in the 3 H incorporation, DNA content in S phase and the expression of PCNA. Transfection of gene encoding TGF β 1 could induce the cells at G0/G1 phase to S1 phase, modulate the replication of DNA through the enhancement of the PCNA expression, increase the content of DNA at S1 phase and promote the proliferation of MSCs. This new molecular tissue engineering approach could be of potential benefit to enhance the repair of damaged articular cartilage, especially those caused by degenerative joint diseases.

Osteogenic Potential of Cultured Bone Marrow Stromal Cells Transfected with Transforming Growth Factor β_1 Gene in vitro

To study the osteogenic potential of cultured bone marrow stromal cells transfected with transforming growth factor β 1 gene in vitro , cultured BMSCs were transfected with the complexes of pcDNA 3 TGF β 1 and Lipofectamine Reagent in vitro . The cell proliferation was detected by MTT method and the morphological features of transfected BMSCs was observed. ALP stains and PNP method were used to measure ALP activity. In addition, the collagen type Ⅰ propeptides and mineralized matrixes were examined by immunohistochemical staining and tetracycline fluorescence labeling respectively. The morphological and biological characters of the transfected BMSCs were similar to those of osteoblasts and the cell proliferation was promoted. The cell layer displayed strong positive reaction for ALP stains and immunohistochemical staining. ALP activity and collagen type Ⅰ expression increased remarkably after transfection. Mineralized matrixes formed earlier and more in transfected BMSCs as compared with control group. It is concluded that transfecting with TGF β 1 gene could promote the osteogenic potential of cultured BMSCs.

The Effect of Simvastatin on mRNA Expression of Transforming Growth Factor-β1,Bone Morphogenetic Protein-2 and Vascular Endothelial Growth Factor in Tooth Extraction Socket

Aim To determine the effect of local simvastatin application on the mRNA expression level of transforming growth factor-β1 （TGF-β1）, bone morphogenetic protein-2 （BMP-2） and vascular endothelial growth factor （VEGF） in the tooth sockets of rat. Methodology Forty-eight male Wistar rats were randomly divided into experimental and control groups （n=24）. Polylactic acid/polyglycolic acid copolymer carriers, with or without simvastatin, were implanted into extraction sockets of right mandibular incisors. The expression of TGF-β1, BMP-2 and VEGF mRNA was determined by in situ hybridization in the tooth extraction socket at five days, one week, two weeks and four weeks after implantation. Results The fusiform stroma cells in the tooth extraction socket began to express TGF-β1, BMP-2 and VEGF mRNA in both experimental and control groups from one week after tooth extraction until the end of experiment. The expression of TGF-131 and BMP-2 mRNA in the experimental group was significantly up-regulated after one, two and four weeks, and expression of VEGF mRNA was significantly increased after one and two weeks compared with that in the control group. Conclusion The findings indicate that local administration of simvastatin can influence alveolar bone remodeling by regulating the expression of a school of growth factors which are crucial to osteogenesis in the tooth extraction socket.

Transforming growth factor-β and toll-like receptor-4 polymorphisms are not associated with fibrosis in haemochromatosis

AIM:To investigate the role of genetic polymorphisms in the progression of hepatic fibrosis in hereditary haemochromatosis.METHODS:A cohort of 245 well-characterised C282Y homozygous patients with haemochromatosis was studied,with all subjects having liver biopsy data and DNA available for testing.This study assessed the association of eight single nucleotide polymorphisms(SNPs)in a total of six genes including toll-like receptor 4(TLR4),transforming growth factor-beta(TGF-β),oxoguanine DNA glycosylase,monocyte chemoattractant protein 1,chemokine C-C motif receptor 2 and interleukin-10 with liver disease severity.Genotyping was performed using high resolution melt analysis and sequencing.The results were analysed in relation to the stage of hepatic fibrosis in multivariate analysis incorporating other cofactors including alcohol consumption and hepatic iron concentration.RESULTS:There were significant associations between the cofactors of male gender(P=0.0001),increasing age(P=0.006),alcohol consumption(P=0.0001),steatosis(P=0.03),hepatic iron concentration(P<0.0001)and the presence of hepatic fibrosis.Of the candidate gene polymorphisms studied,none showed a significant association with hepatic fibrosis in univariate or multivariate analysis incorporating cofactors.We also specifically studied patients with hepatic iron loading above threshold levels for cirrhosis and compared the genetic polymorphisms between those with no fibrosis vs cirrhosis however there was no significant effect from any of the candidate genes studied.Importantly,in this large,well characterised cohort of patients there was no association between SNPs for TGF-βor TLR4and the presence of fibrosis,cirrhosis or increasing fibrosis stage in multivariate analysis.CONCLUSION:In our large,well characterised group of haemochromatosis subjects we did not demonstrate any relationship between candidate gene polymorphisms and hepatic fibrosis or cirrhosis.

Study of Rat Osteoblasts Transfected by Transforming Growth Factorβ_(1)Gene

Summary:In order to investigate the effect of TGFβ_(1) gene transfer on the biological characteristics,the effects of gene transfer and supernatant of transfected osteoblasts on the proliferation and ALP activity of osteoblasts were detected by ^(3)H-TdR and MTT.Our results showed that TGFβ_(1) gene transfer had no effect on the biological characteristics and the activated supernatant of transfected osteoblasts stimulated proliferation and inhibited ALP activity of osteoblasts.TGFβ_(1) gene transfer could promote the expression of TGFβ_(1) and the biological characteristics of transfected osteoblasts were stable,which might be helpful for gene therapy of bone defects in vivo.

Vascular endothelial growth factor A, secreted in response to transforming growth factor-β1 under hypoxic conditions, induces autocrine effects on migration of prostate cancer cells

Hypoxia and transforming growth factor-β1 （TGF-β1） increase vascular endothelial growth factor A （VEGFA） expression in a number of malignancies. This effect of hypoxia and TGF-β1 might be responsible for tumor progression and metastasis of advanced prostate cancer. In the present study, TGF-β1 was shown to induce VEGFA165 secretion from both normal cell lines （HPV7 and RWPE1） and prostate cancer cell lines （DU 145 and PC3）. Conversely, hypoxia-stimulated VEGFA165 secretion was observed only in prostate cancer cell lines. Hypoxia induced TGF-β1 expression in PC3 prostate cancer cells, and the TGF-β1 type I receptor （ALK5） kinase inhibitor partially blocked hypoxia-mediated VEGFA16s secretion. This effect of hypoxia provides a novel mechanism to increase VEGFA expression in prostate cancer cells. Although autocrine signaling of VEGFA has been implicated in prostate cancer progression and metastasis, the associated mechanism is poorly characterized. VEGFA activity is mediated via VEGF receptor （VEGFR） 1 （Fit-l） and 2 （FIk-I/KDR）. Whereas VEGFR-1 mRNA was detected in normal prostate epithelial cells, VEGFR-2 mRNA and VEGFR protein were expressed only in PC3 cells. VEGFA165 treatment induced phosphorylation of extracellular signal-regulated kinase 1/2 （ERKI/2） in PC3 cells but not in HPV7 cells, suggesting that the autocrine function of VEGFA may be uniquely associated with prostate cancer. Activation of VEGFR-2 by VEGFA165 was shown to enhance migration of PC3 cells. A similar effect was also observed with endogenous VEGFA induced by TGF-β1 and hypoxia. These findings illustrate that an autocrine loop of VEGFA via VEGFR-2 is critical for the tumorigenic effects of TGF-β1 and hypoxia on metastatic prostate cancers.

The involvement of p38 MAPK in transforming growth factor β1-induced apoptosis in murine hepatocytes

We reported in this manuscript that TGF-beta1 induces apoptosis in AML12 murine hepatocytes, which is associated with the activation of p38 MAPK signaling pathway. SB202190, a specific inhibitor of p38 MAPK, strongly inhibited the TGF-beta1-induced apoptosis and PAI-1 promoter activity. Treatment of cells with TGF-beta1 activates p38. Furthermore, over-expression of dominant negative mutant p38 also reduced the TGF-beta1-induced apoptosis. The data indicate that the activation of p38 is involved in TGF-beta1-mediated gene expression and apoptosis.

Cloning and Expression of Rat Transforming Growth Factor β1 cDNA in Osteoblasts

Summary: Rat transforming growth factor β1 (rTGFβ1) cDNA from rat lymphocytes was cloned by RT-PCR and inserted into pcDNA3 to construct an eukaryotic expression vector, which was named pcDNA3-TGFβ1. The cloned gene was confirmed to code rat TGFβ1 by restriction enzyme analysis. pcDNA3-TGFβ1 plasmid was transfected into rat osteoblasts by using liposome-mediated gene transfer technique and the expression of TGFβ1 was detected by using irnmunohistochemical staining assay. It was found that the rat TGFβ1 expression product was obviously detectable in the transfected osteoblasts in 48 h. High expression of TGFβ1 was obtained in the rat osteoblasts in which the constructed TGFβ1 expression vector was transfected.

Expression of Transforming Growth Factor β_(1) in Mesenchymal Stem Cells: Potential Utility in Molecular Tissue Engineering for Osteochondral Repair

The feasibility of using gene therapy to treat full-thickness articular cartilage defects was investigated with respect to the transfection and expression of exogenous transforming growth factor(TGF)-β_(1)genes in bone marrow-derived mesenchymal stem cells(MSCs)in vitro.The full-length rat TGF-β_(1)cDNA was transfected to MSCs mediated by lipofectamine and then selected with G418,a synthetic neomycin analog.The transient and stable expression of TGF-β_(1)by MSCs was detected by using immunohistochemical staining.The lipofectamine-mediated gene therapy efficiently transfected MSCs in vitro with the TGF-β_(1)gene causing a marked up-regulation in TGF-β_(1)expression as compared with the vector-transfected control groups,and the increased expression persisted for at least 4 weeks after selected with G418.It was suggested that bone marrow-derived MSCs were susceptible to in vitro lipofectamine mediated TGF-β_(1)gene transfer and that transgene expression persisted for at least 4 weeks.Having successfully combined the existing techniques of tissue engineering with the novel possibilities offered by modern gene transfer technology,an innovative concept,i.e.molecular tissue engineering,are put forward for the first time.As a new branch of tissue engineering,it represents both a new area and an important trend in research.Using this technique,we have a new powerful tool with which:(1)to modify the functional biology of articular tissue repair along defined pathways of growth and differentiation and(2)to affect a better repair of full-thickness articular cartilage defects that occur as a result of injury and osteoarthritis.

子宫内膜异位症不同r-AFS分期患者血清Furin,TGF-β,VEGF,netrin-1水平表达及Furin基因P1启动区r2071410 C/T位点多态性分析

目的了解子宫内膜异位症(endometriosis,EMT)不同r-AFS分期患者血清弗林蛋白酶(Furin)、肿瘤生长因子-β(tumor growth factor-β,TGF-β)、血管生长因子(vascular endothelial growth factor,VEGF)及神经轴突导向因子-1(neuron towards axon guidance factor-1,netrin-1)水平表达及Furin基因P1启动区r2071410 C/T位点多态性,探讨其与深圳地区EMT发病的相关性。方法选取2021年5月~2023年1月深圳市龙华区人民医院确诊的EMT患者102例为EMT组,并根据r-AFs分期法将EMT组分为I~II期和III~IV期。同时收集同期非EMT患者78例为对照组。采用酶联免疫吸附法(enzyme-linked immunosorbent assay,ELISA)检测血清Furin,TGF-β,VEGF及netrin-1水平,并采用反转录-实时荧光定量聚合酶链反应法(reverse transcription-real time quantitative polymerase chain reaction,RT-qPCR)分析Furin基因P1启动区r2071410 C/T位点多态性。结果EMT组患者血清Furin(140.84±47.02pg/ml),TGF-β(376.46±82.36ng/L)和VEGF水平(167.67±53.02ng/L)明显高于对照组(55.49±13.67pg/ml,216.37±15.04ng/L,102.27±8.45ng/L),而netrin-1水平(48.37±15.20pg/ml)明显低于对照组(165.85±15.63pg/ml),差异具有统计学意义(t=28.409,20.347,16.915,36.653,均P<0.05)。III~IV期患者血清Furin(192.41±20.62pg/ml),TGF-β(452.61±72.03ng/L)和VEGF水平(201.84±28.01ng/L)明显高于I~II期(78.05±16.54pg/ml,283.75±56.92ng/L,126.07±19.35ng/L),而netrin-1水平(37.95±11.34pg/ml)明显低于I~II期(61.05±9.52pg/ml),差异有统计学意义(t=31.071,18.054,19.183,21.625,均P<0.05)。经Pearson/Spearman相关性分析结果显示,Furin与TGF-β,VEGF水平及临床分期呈正相关(r=0.6149,0.7526,0.7905,均P<0.05),而与netrin-1水平呈负相关(r=-0.6701,均P<0.05)。EMT组患者Furin基因P1启动区r2071410 C/T位点TT基因型和T等位基因频率(42.16%,55.39%)明显高于对照组(7.69%,19.87%),且III~IV期TT基因型和T等位基因频率(51.79%,65.18%)比I~II期(30.43%,43.48%)明显升高,差异具有统计学意义(χ^(2)=26.500,46.472,4.721,9.626,均P<0.05)。EMT组不同基因型患者血清Furin水平差异具有统计学意义(F=51.286,P<0.001),其中TT基因型患者血清Furin水平(216.29±68.53pg/ml)明显高于CC(83.04±21.37pg/ml)和CT基因型(89.18±20.95pg/ml),差异具有统计学意义(t=27.146,25.719,均P<0.01),但CC与CT基因型之间差异无统计学意义(t=1.326,P>0.05)。结论EMT患者血清Furin水平明显升高,且与TGF-β,VEGF,netrin-1水平及临床分期呈一定相关性;同时Furin基因P1启动区r2071410 C/T位点呈多态性分布,其中TT基因型患者血清Furin水平升高更为明显,可能与深圳地区EMT发病有关。

PVT1通过TGF-β1/SMAD通路促进子宫内膜基质细胞过度纤维化的研究

目的探讨长链非编码RNA(lncRNA)浆细胞瘤多样异位基因1(PVT1)在调控子宫内膜基质细胞纤维化中的病理生理作用及分子机理。方法通过实时荧光定量聚合酶链反应(qRT-PCR)检测人子宫内膜基质细胞(HESCs)中PVT1、胶原蛋白Ⅰ、胶原蛋白Ⅲ、转化生长因子-β1(TGF-β1)、SMAD2及SMAD3的表达水平。结果PVT1过表达促进HESCs增殖(P<0.05),而PVT1沉默抑制HESCs增殖(P<0.05)。过表达PVT1在HESCs中上调胶原蛋白Ⅰ和胶原蛋白ⅢmRNA的表达(P<0.05),而PVT1被敲除时,胶原蛋白Ⅰ和胶原蛋白ⅢmRNA的表达水平被显著下调(P<0.05)。过表达PVT1在HESCs中可以进一步上调TGF-β1/SMAD信号相关基因(TGF-β1、SMAD2、SMAD3)的表达(P<0.05)。当PVT1被敲除时,TGF-β1/SMAD信号相关基因胶原蛋白Ⅰ和胶原蛋白ⅢmRNA的表达水平被显著下调(P<0.05)。PVT1可诱导HESCs上清液中TGF-β1的产生(P<0.05)。结论PVT1可通过TGF-β1/SMAD通路促进子宫内膜基质细胞过度纤维化而产生胶原蛋白。同时,PVT1可能是一个用于治疗子宫内膜粘连的新靶点。

Genetic expression of Col-2A and Col-10A as a function of administration of IGF-1 &TGF-<i>β</i>with and without anterior mandibular repositioning appliance on the growth of mandibular condylar cartilage in young rabbit

New Zealand (NZ) young rabbits with the administration of insulin-like growth factor (IGF-1) and transforming growth factor-β (TGF-β) with and without mandibular anterior repositioning appliances are explored for the growth of the mandibular condylar cartilage (MCC). 32 growing NZ and rabbits were divided into 4 groups: the group with saline injection in TMJ, the group which received growth factor injection in TMJ, the group which received anterior positioning appliance and the group which received growth factors injection as well as mandibular repositioning appliance. Gene expression was studied by real-time RT-PCR and cartilage growth by histomorphometry. Administration of growth factors along with mandibular repositioning appliances has induced 1) 1.70-fold expression of Col-2Agene (p value < 0.0005) and 2) 1.47-fold expression of Col-10Agene (p value < 0.0005). In contrast, administration of only mandibular repositioning appliances induced 1) 1.28-fold expression of Col-2Agene (p value < 0.0005) and 2) merely 0.62-fold expression of Col-10Agene (p value < 0.0005), while administration of growth factors only induced 1) mere 0.56-fold expression of Col-2Agene (p value 10A gene (p value growth factors along with mandibular repositioning appliances causes an increase in genetic expressions which have been corroborated by histomorphometry and validated by statistical analysis, during an accelerated growth of mandibular condylar cartilage. Administration of growth factors in the TMJ could provide a synergistic role along with mandibular repositioning appliances for treatment of mandibular retrognathism as well as disorders on the MCC.

γ-干扰素基因修饰肝细胞对感染日本血吸虫小鼠TGF-β_1及其受体的影响

目的： 探讨γ－干扰素 （ＩＦＮ－γ） 基因治疗对感染日本血吸虫小鼠转化生长因子－β１ （ＴＧＦ－β１） 及其受体的影响与抗肝纤维化作用的关系。方法： 将小鼠ＩＦＮ－γ基因重组腺病毒载体转染的肝细胞经脾移植到感染日本血吸虫尾蚴１６ ｗｋ 的小鼠， 采用ＥＬＩＳＡ、免疫组化和斑点杂交方法分析小鼠血清ＩＦＮ－γ与ＴＧＦ－β１ 表达的关系， 小鼠肝内ＩＦＮ－γ、ＴＧＦ－β１、ＴＧＦ－βＲＩＩ与Ⅰ、Ⅲ型胶原表达的关系。结果： ＩＦＮ－γ基因修饰的肝细胞经脾移植后能有效地表达， 显著地降低ＴＧＦ－β１ 、ＴＧＦ－βＲＩＩ的表达和Ⅰ、Ⅲ型胶原的含量。结论： ＩＦＮ－γ基因治疗能有效地发挥抗血吸虫病肝纤维化作用， 可能与降低ＴＧＦ－β１及其受体有关。

TGF-β_1基因启动子-800GA、-509C/T多态性与食管癌的研究

目的 :研究转化生长因子 β1 (TGF-β1 )基因启动子多态性各等位基因及基因型在食管癌患者中的分布频率 ,初步分析其基因型及血清水平与食管癌的相关性。方法 :采用聚合酶链反应 限制性片段长度多态性 (PCR-RFLP)技术 ,检测 118例食管癌患者和 130例正常对照组TGF-β1 的基因多态性 ,包括TGF-β1 基因启动子 -80 0G A、 5 0 9C T位点 ,同时采用ELISA检测血清TGF β1 水平。结果 :食管癌患者血清TGF-β1 水平显著高于对照组 (P <0.0 1) ,TGF-β1 基因 80 0G A位点多态性在食管癌组和正常人群中的分布差异无显著性 (P >0. 0 5 ) ,而TGF-β1 基因 5 0 9C T多态性各等位基因及基因型频率在两组人群中的分布差异存在显著性 (P <0.0 5 ) ;等位基因频率的相对风险分析发现 ,T等位基因携带者患食管癌的风险是C等位基因的 1 6 2 4倍 (OR =1 6 2 4 ,95 %CI:1.134～ 2.32 4 ) ,携带T等位基因的食管癌患者血清TGF-β1 水平显著高于不携带者 (5 0 .97± 8.91μg LVS 4 4 2 3± 8 5 4 μg L ,P <0 .0 1)。 结论 :TGF-β1 基因- 5 0 9C T多态性与食管癌的发病具有相关性 ,其中T等位基因可能是食管癌发病的遗传易感基因 ;携带T等位基因的个体可能通过促进TGF-β1

TGF-β_1基因多态性与乙型肝炎肝硬化的相关性研究

目的探讨转化生长因子-β1(TGF-β1)基因多态性是否与慢性HBV感染人群肝硬化发生的遗传易感相关。方法收集173例中国汉族慢性HBV感染患者(肝硬化组42例和非肝硬化组131例)和52例健康对照者的外周血标本,提取白细胞DNA,基因直接测序法检测TGF-β1基因4个多态性(869T/C、915G/C、-800 G/A、-509 C/T),ELISA法检测TGF-β1血清浓度,比较各组TGF-β1基因型分布频率、等位基因频率及TGF-β1血清水平的差异。结果 (1)乙型肝炎肝硬化组TGF-β1869位点以TT基因型为主(47.6%),高于非肝硬化组(25.2%)和对照组(19.2%),差异有统计学意义(P<0.05);869T等位基因频率(63.1%)明显高于正常对照组(44.2%),差异有统计学意义(P<0.05),乙型肝炎肝硬化组与慢性HBV感染非肝硬化组(53.8%)、慢性HBV感染非肝硬化组与正常组869T等位基因携带率相比,差异无统计学意义(P>0.05)。(2)所检其余多态性位点基因型及基因频率未见组间统计学差异。(3)869T/C不同基因型患者的血清TGF-β1水平不一,T/T型携带者较T/C和C/C型可见明显增高(P<0.017)。结论 TGF-β1869T可能与汉族人群乙型肝炎肝硬化的遗传易感相关,其机制可能与该多态性对TGF-β1血清水平的影响有关。

贵州汉族TGF-β_1基因多态性与系统性红斑狼疮相关性的研究

目的:探讨转化生长因子-β1(TGF-β1)基因启动子-509C/T多态性与贵州汉族人群系统性红斑狼疮(SLE)的相关性。方法:采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术,分析80例SLE患者及95例正常对照组的TGF-β1基因启动子-509C/T多态性。结果:SLE组与正常对照组-507C/T基因型频率分布有差异(P<0.05),-509CC基因型SLE组高于对照组(35% vs 21.1%),而-509TT型SLE组明显低于正常对照组(18.75% vs 36.8%);SLE患者组-509位点的等位基因频率与正常对照组比较差异也有显著性(P<0.005),SLE组C等位基因频率显著高于对照组(58.1% vs 42.1%),T等位基因频率低于对照组(41.9% vs 57.9%)。结论:贵州汉族人群TGF-β1基因启动子-509C/T多态性与SLE显著相关。

TGF-β_1基因T29→C多态性与2型糖尿病肾病的相关性

应用PCR-RFLP技术检测福建地区167例2型糖尿病患者(其中80例合并糖尿病肾病)和62名健康对照者TGF-β1基因T29→C多态性,结果显示,C等位基因可能与糖尿病肾病发病相关。

大鼠半乳糖性白内障晶状体中TGF-β_1基因的表达

目的 研究转化生长因子 β1(TGF β1)基因在大鼠白内障发生过程中的表达。方法 给 3周龄大鼠单眼球后注射 2 0 %半乳糖生理盐水诱导白内障的发生 ,运用RT PCR方法测定在不同时相大鼠晶状体中TGF β1基因的表达。结果 半乳糖注射后晶状体上皮细胞TGF β1mRNA于 8h开始上升 ,2 4h达高峰 ,是正常对照的 4倍 ,2d后迅速下降 ,4d完全恢复到正常水平。结论 在白内障形成的早期 ,晶状体细胞中TGF β1呈高表达 ,提示TGF