血吸虫病肝纤维化患者转化生长因子β_1mRNA的水平及其临床意义

目的：研究血吸虫病患者 Ｔ Ｇ Ｆβ１ ｍ Ｒ Ｎ Ａ 水平及其临床意义。方法：用 Ｒ Ｔ Ｐ Ｃ Ｒ 加 ｄｏｔｂｌｏｔ法测定血吸虫病患者 Ｐ Ｂ Ｍ Ｃ中 Ｔ Ｇ Ｆβ１ ｍ Ｒ Ｎ Ａ 水平,与肝硬变和肝癌患者作比较,并研究了部分肝脏组织（肝癌患者１６ 例,肝血管瘤患者正常肝组织 ５ 例）中 Ｔ Ｇ Ｆβ１ ｍ Ｒ Ｎ Ａ 水平与 Ｐ Ｂ Ｍ Ｃ中水平的关系。同时,测定血清中 Ｈ Ａ、 Ｌ Ｎ、 ＣｏｌⅠⅤ和 Ｐ ＣⅢ水平,作为衡量肝纤维化活动与否的指标。结果： Ｐ Ｂ Ｍ Ｃ内 Ｔ Ｇ Ｆβ１ ｍ Ｒ Ｎ Ａ 水平在晚期血吸虫病患者组（ｎ＝ ２１,１２６±０１４）,肝硬变患者组（ｎ＝ １５,２０５±０８１）和肝癌患者组（ｎ＝ ２５,１８３±１２９）均显著高于正常对照组（ｎ＝ １６,０６２±０４０）（ Ｐ＜ ００５）。其中晚期血吸虫病患者组又显著低于肝硬变患者组或肝癌患者组（ Ｐ＜ ００５）,后两组差异无显著性（ Ｐ＞ ００５）。肝组织与 Ｐ Ｂ Ｍ Ｃ内 Ｔ Ｇ Ｆβ１ ｍ Ｒ Ｎ Ａ 水平差别无统计学意义（ Ｐ＞ ００５）。血清 Ｈ Ａ、 ＣｏｌⅣ和 Ｌ Ｎ 异常组的 Ｔ Ｇ Ｆβ１ ｍ Ｒ Ｎ Ａ 水平显著高于正常组（ Ｐ＜ ００５）。结论： Ｐ     

血吸虫病肝纤维化患者转化生长因子β_1mRNA的水平及其临床意义

目的：研究血吸虫病患者 Ｔ Ｇ Ｆ β１ ｍ Ｒ Ｎ Ａ 水平及其临床意义。方法：用 Ｒ Ｔ Ｐ Ｃ Ｒ 加 ｄｏｔｂｌｏｔ法测定血吸虫病患者 Ｐ Ｂ Ｍ Ｃ中 Ｔ Ｇ Ｆ β１ ｍ Ｒ Ｎ Ａ 水平,与肝硬变和肝癌患者作比较,并研究了部分肝脏组织（肝癌患者１６ 例,肝血管瘤患者正常肝组织 ５ 例）中 Ｔ Ｇ Ｆ β１ ｍ Ｒ Ｎ Ａ 水平与 Ｐ Ｂ Ｍ Ｃ中水平的关系。同时,测定血清中 Ｈ Ａ、 Ｌ Ｎ、 Ｃｏｌ ⅠⅤ和 Ｐ ＣⅢ水平,作为衡量肝纤维化活动与否的指标。结果： Ｐ Ｂ Ｍ Ｃ内 Ｔ Ｇ Ｆ β１ ｍ Ｒ Ｎ Ａ 水平在晚期血吸虫病患者组（ｎ＝ ２１,１２６±０１４）,肝硬变患者组（ｎ＝ １５,２０５±０８１）和肝癌患者组（ｎ＝ ２５,１８３±１２９）均显著高于正常对照组（ｎ＝ １６,０６２±０４０）（ Ｐ＜ ００５）。其中晚期血吸虫病患者组又显著低于肝硬变患者组或肝癌患者组（ Ｐ＜ ００５）,后两组差异无显著性（ Ｐ＞ ００５）。肝组织与 Ｐ Ｂ Ｍ Ｃ内 Ｔ Ｇ Ｆ β１ ｍ Ｒ Ｎ Ａ 水平差别无统计学意义（ Ｐ＞ ００５）。血清 Ｈ Ａ、 Ｃｏｌ Ⅳ和 Ｌ Ｎ 异常组的 Ｔ Ｇ Ｆ β１ ｍ Ｒ Ｎ Ａ 水平显著高于正常组（ Ｐ＜ ００５）。结论： Ｐ     

类风湿关节炎滑膜组织转化生长因子β1 转化生长因子β受体Ⅰ及转化生长因子β1 mRNA的表达

类风湿关节炎 (ｒｈｅｕｍａｔｏｉｄａｒｔｈｒｉｔｉｓ,ＲＡ)的基本病理改变为关节滑膜慢性炎症形成侵袭性血管翳 ,破坏软骨、骨与周围组织。在参与免疫炎症反应的各种因子中 ,转化生长因子 (ＴＧＦ) β1为一种重要的有双向作用的细胞因子 ,可促进炎症细胞活化、浸润 ,又可促进血管增生、组织修复。本研究应用免疫组织化学ＳＡＢＣ法与地高辛标记原位杂交法对ＲＡ滑膜组织中ＴＧＦ β1、转化生长因子 β受体Ⅰ (ＴＧＦ βＲⅠ )、ＴＧＦ β1ｍＲＮＡ的表达分布情况进行分析 ,以探讨它们与ＲＡ发病机制和治疗的关系。1　材料与方法1 1　标…     

转化生长因子β1及虫草多糖对大鼠肝纤维化形成的影响

目的探讨转化生长因子β１（ｔｒａｎｓｆｏｒｍｉｎｇｇｒｏｗｔｈｆａｃｔｏｒβ１，ＴＧＦβ１）及其受体１（ＴＧＦβＲ１）在免疫性大鼠肝纤维化形成中的作用及虫草多糖对其影响。方法以牛血清白蛋白（ｂｏｖｉｎｅｓｅｒｕｍａｌｂｕｍｉｎ，ＢＳＡ）制备免疫性大鼠肝纤维化，攻击注射８周后给予虫草多糖（６０ｍｇ／ｋｇ）保护，继续攻击注射４次，用药至末次注射３周后（共３４天）；用免疫组化法观察ＴＧＦβ１、ＴＧＦβＲ１、肝星状细胞及Ⅰ、Ⅲ型胶原的变化。结果攻击注射ＢＳＡ８月后，大鼠已形成典型的肝纤维化；纤维隔中ＴＧＦβ１及ＴＧＦβＲ１阳染增强，后者阳染强度与胶原增生程度有相关性；肝星状细胞显著增多，Ⅰ、Ⅲ型胶原及肝羟脯氨酸含量显著增加。虫草多糖组对应指标的变化均显著轻于对照组。结论ＴＧＦβ１与ＴＧＦβＲ１表达的增加是ＢＳＡ免疫性大鼠肝纤维化发生发展的病理基础之一；虫草多糖可显著改善免疫性大鼠肝纤维化的病理变化。     

慢性肝病患者血清转化生长因子β_1水平与肝纤维化的关系

目的 探讨血清转化生长因子β_1(TGF-β_1)水平与肝纤维化的关系及在肝纤维化中的诊断价值。方法对139例肝病患者血清采用ELISA法检测TGF-β_1水平,并同时采用放射免疫法检测血清HA、LN、Ⅳ-C等肝纤维化血清学指标。结果 随着病情加重、肝纤维化程度加深,血清TGF-β_1逐渐升高,以肝硬变组最明显;血清TGF-β_1水平与血清HA、LN、Ⅳ-C均呈明显的正相关,且与Ⅳ_C相关更密切。结论 血清TGF-β_1与肝纤维化有密切联系,其血清水平可反映肝纤维化的程度,可作为诊断肝纤维化的一项可靠的新的血清学指标。     

糖尿病大鼠肾小球产生转化生长因子β的研究

多肽生长因子合成和活性的异常是导致糖尿病肾病系膜区扩张的机理之一.本文检测了糖尿病大鼠肾小球TOFB的水平,并探讨了体外高糖环境对系膜细胞产生TGFβ的影响.制备STZ诱发的糖尿病模型,4周后用生物学方法检测肾小球培养上清中的TGFβ水平,结果发现糖尿病大鼠肾小球分泌的总TGFβ及活性TGFβ均比对照显著增加,其中活性TGFβ水平的增加更为明显;体外高糖培养后的系膜细胞产生的总TGFβ明显下降,而活性TGFβ却有上升.结果表明高糖环境下肾小球和系膜细胞确实存在着TGFβ分泌和激活的异常,TGFβ可能参与了糖尿病肾病系膜区扩张的形成。     

转化生长因子β_1对胃癌细胞表皮生长因子受体表达的影响和定量研究

用转化生长因子β_1(transforming growth factor β_1,TGFβ_1)作用于入胃腺癌细胞(SGC-7901),48小时后收集细胞爬片。用抗表皮生长因子受体(epidermal growth factor receptor,EGFR)的单抗和免疫组化SABC法及图像分析,发现TGFβ_1作用的胃癌细胞EGFR表达量(107.943±0.202)低于对照细胞(114.298±0.475),差异显著(P<0.05),研究结果提示,TGFβ_1对胃癌细胞增殖的抑制作用可能与其影响EGFR表达数量有关。     

碱性成纤维细胞生长因子和转化生长因子β_1表达与心肌肥大的研究

目的 :探讨碱性成纤维细胞生长因子 (b FGF)和转化生长因子β1 (TGFβ1 )在人体超负荷性心肌肥厚发生机制中的作用。方法 :用免疫组织化学及原位杂交技术检测 32例 (左、右室心肌各 16例 )肥大心肌组织中b FGF和 TGFβ1 的表达。结果 :无论是压力还是容量超负荷都可使心肌细胞 b FGF、TGFβ1 表达增加 (P <0 .0 5 ,<0 .0 1)。结论 :b FGF和 TGFβ1 可能是介导临床超负荷性心肌肥厚发生的因素之一。     

转化生长因子β和肺纤维化

转化生长因子β(transforming growth factor-β,TGF-β)是启动和终止炎症和组织修复的调节因子,是参与调控肺纤维化发生的细胞因子.TGF-β亚单位功能与其种类以及与受体的亲和力有密切关系.TGF-β的信号通路在纤维化的发生发展中起重要作用.     

缺氧对大鼠肝细胞转化生长因子β1表达的影响

目的:探讨缺氧对转化生长因子β1(transform-inggrowthfactor-β1,TGF-β1)在肝细胞表达的影响.方法:选择SD大鼠20只,采用气管阻塞的方法建立轻、中、重度的缺氧模型,15min和60min采集肝脏标本,用免疫组化技术SABC法检测肝细胞转化生长因子β1表达的变化.结果:在正常肝脏中TGF-β1极少表达或无表达(15和60min分别为3.6±1.9,3.6±1.9),随着缺氧时间的延长与缺氧程度的加重,肝细胞转化生长因子β1表达逐渐增加(轻度缺氧15和60min分别为8.5±2.0,15.2±3.1;中度缺氧15和60min分别为18.4±3.5,63.7±3.8;重度缺氧15和60min分别为68.9±3.2,86.7±3.6).结论:大鼠缺氧条件下肝脏TGF-β1表达增加可促进细胞外基质的合成,有利于肝细胞的再生与修复.     

The significance of serum transforming growth factor beta 1 in detecting of gastric and colon cancers

BACKGROUND/AIMS: TGF-beta1 is a growth factor with wide ranging effects on proliferation, differentiation, immune suppression, apoptosis and matrix remodeling. We aimed to clarify the clinical significance of circulating levels of TGF-beta1 as a tumor marker in gastrointestinal tract cancers by comparing it to CEA across a range of parameters such as cancer type and severity. METHODOLOGY: Sera collected from patients with gastrointestinal tract cancers (32 gastric, 36 colon) and from 25 healthy volunteers were analyzed for TGF-beta1 and CEA. Relations between serum TGF-beta1 levels and tumor stage and tumor grade were also evaluated. RESULTS: Mean serum TGF-beta1 levels were higher in patients with gastric or colon cancer compared to the control group (p = 0.001). In both types of cancer there were no differences in TGF-beta1 levels associated with serosal involvement, lymph node involvement, vascular invasion, distant metastasis or tumor size. Mean serum TGF-beta1 levels were also not statistically different across histopathological tumor grades in either type of cancer. The sensitivity of TGF-beta1 was higher in patients with gastric cancer than in patients with colon cancer. TGF-beta1 had greater sensitivity than CEA in gastric cancer patients. CONCLUSIONS: TGF-beta1 has higher sensitivity in gastric and colon cancers. Since it may be increased even in cancer without closed and distant metastasis, TGF-beta1 may be used as a tumor marker and combined with CEA particularly in gastric cancers.     

Iodide induces transforming growth factor beta 1 (TGF-beta 1) mRNA in sheep thyroid cells.

We examined TGF-beta mRNA levels in primary sheep thyroid cell cultures to determine whether the inhibitory effects of iodide on thyroid cells could be explained by an induction of TGF-beta mRNA and if this induction was mediated by iodine organification. Thyroid cells were incubated with TSH and five additives (insulin, somatostatin, growth hormone, transferrin, and glycyl-L-histidyl-L-lysin) for 2-3 weeks and then were exposed to sodium iodide (NaI) or 1-methylimidazole-2-thiol (methimazole, MMI), or both for 72 h. Iodide at 10(-6) M and 10(-4) M significantly increased the amount of TGF-beta mRNA as determined by Northern blot analysis with a rat TGF-beta 1 cDNA probe. This increase in TGF-beta 1 mRNA was abolished by the addition of methimazole, an inhibitor of organification. These data indicate that the effects of iodide on thyroid growth and function may be mediated by a process that involves organification of iodide and increases in TGF-beta 1 mRNA levels.     

The recombinant proregion of transforming growth factor beta1 (latency-associated peptide) inhibits active transforming growth factor beta1 in transgenic mice.

All three isoforms of transforming growth factors beta (TGF-betal, TGF-beta2, and TGF-beta3) are secreted as latent complexes and activated extracellularly, leading to the release of the mature cytokines from their noncovalently associated proregions, also known as latency-associated peptides (LAPs). The LAP region of TGF-beta1 was expressed in a baculovirus expression system and purified to homogeneity. In vitro assays of growth inhibition and gene induction mediated by TGF-beta3 demonstrate that recombinant TGF-beta1 LAP is a potent inhibitor of the activities of TGF-betal, -beta2, and -beta3. Effective dosages of LAP for 50% neutralization of TGF-beta activities range from 4.7- to 80-fold molar excess depending on the TGF-beta isoform and activity examined. Using 125I-labeled LAP, we show that the intraperitoneal application route is effective for systemic administration of LAP. Comparison of concentrations of LAP in tissues shows a homogenous pattern in most organs with the exception of heart and muscle, in which levels of LAP are 4- to 8-fold lower. In transgenic mice with elevated hepatic levels of bioactive TGF-betal, treatment with recombinant LAP completely reverses suppression of the early proliferative response induced by TGF-beta1 in remnant livers after partial hepatectomy. The results suggest that recombinant LAP is a potent inhibitor of bioactive TGF-beta both in vitro and in vivo, after intraperitoneal administration. Recombinant LAP should be a useful tool for novel approaches to study and therapeutically modulate pathophysiological processes mediated by TGF-beta3.     

Arrest of endotoxin-induced hypotension by transforming growth factor beta1.

Septic shock is a cytokine-mediated process typically caused by a severe underlying infection. Toxins generated by the infecting organism trigger a cascade of events leading to hypotension, to multiple organ system failure, and frequently to death. Beyond supportive care, no effective therapy is available for the treatment of septic shock. Nitric oxide (NO) is a potent vasodilator generated late in the sepsis pathway leading to hypotension; therefore, NO represents a potential target for therapy. We have previously demonstrated that transforming growth factor (TGF) beta1 inhibits inducible NO synthase (iNOS) mRNA and NO production in vascular smooth muscle cells after its induction by cytokines critical in the sepsis cascade. Thus, we hypothesized that TGF-beta1 may inhibit iNOS gene expression in vivo and be beneficial in the treatment of septic shock. In a conscious rat model of septic shock produced by Salmonella typhosa lipopolysaccharide (LPS), TGF-beta1 markedly reduced iNOS mRNA and protein levels in several organs. In contrast, TGF-beta1 did not decrease endothelium-derived constitutive NOS mRNA in organs of rats receiving LPS. We also performed studies in anesthetized rats to evaluate the effect of TGF-beta1 on the hemodynamic compromise of septic shock; after an initial 25% decrease in mean arterial pressure, TGF-beta1 arrested LPS-induced hypotension and decreased mortality. A decrease in iNOS mRNA and protein levels in vascular smooth muscle cells was demonstrated by in situ hybridization and NADPH diaphorase staining in rats treated with TGF-beta1. Thus these studies suggest that TGF-beta1 inhibits iNOS in vivo and that TGF-beta1 may be of future benefit in the therapy of septic shock.     

Involvement of alphavbeta5 integrin-mediated activation of latent transforming growth factor beta1 in autocrine transforming growth factor beta signaling in systemic sclerosis fibroblasts

OBJECTIVE: To confirm the involvement of alphavbeta5 in the self-activation system in systemic sclerosis (SSc) fibroblasts. METHODS: Levels of alphavbeta5 expression were analyzed by immunoprecipitation. The promoter activity of the human alpha2(I) collagen gene was determined by transient transfection assay. Phosphorylation levels and DNA binding ability of Smad3 were investigated by immunoprecipitation and DNA affinity precipitation, respectively. The localization of active transforming growth factor beta (TGFbeta) was determined by coculture assay using TMLC cells (mink lung epithelial reporter cells that stably express a portion of the plasminogen activator inhibitor 1 promoter). The morphologic features of cells were determined by immunofluorescence analysis. RESULTS: Levels of alphavbeta5 expression were significantly elevated in SSc fibroblasts compared with normal fibroblasts. Treatment with anti-alphavbeta5 antibody or beta5 antisense oligonucleotide significantly reduced human alpha2(I) collagen gene promoter activity in SSc fibroblasts. In SSc fibroblasts pretreated with TGFbeta1 antisense oligonucleotide, the exogenous latent TGFbeta1 stimulation significantly increased human alpha2(I) collagen gene promoter activity; this effect was significantly reduced in the presence of anti-alphavbeta5 antibody. Phosphorylation levels and DNA binding ability of Smad3 in SSc fibroblasts were significantly reduced by treatment with beta5 antisense oligonucleotide. The luciferase activity of TMLC cells cocultured with SSc fibroblasts was significantly elevated compared with that of TMLC cells cocultured with normal fibroblasts and was significantly reduced in the presence of anti-alphavbeta5 antibody. Anti-alphavbeta5 antibody reversed the myofibroblastic features of SSc fibroblasts. CONCLUSION: Up-regulated expression of alphavbeta5 contributes to the establishment of autocrine TGFbeta signaling in SSc fibroblasts through activation of endogenous latent TGFbeta1.