Study on VEGF, bFGF and TGF-β1 in the Endometriumof Norplant Users

Objective To investigate the relationship between abnormal uterus bleeding and en dometrium vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) as well as transforming growth factor-β1(TGF-β1) expressions among Nor plant users. Materials & Methods Thirty-six endometrium samples from Norplant users with nor mal and abnormal bleeding were studied morphologically and immunohistochemically for VEGF, bFGF and TGF-β1 expression. Six normal samples of proliferate endome tria were studied as control. Results In the Norplant users, the characteristics of endometrium changed and glands decreased in numbers. The VEGF expression in epithelium and vascular en dothelium was lower in those with abnormal uterine bleeding. However, no difference was detected on bFGF and TGF-β1 expression. Conclusion The decline of VEGF expression may relate to the abnormal uterine bleed ing in Norplant users.     

Influence of High Level TGF-β1 on Scleral Thickness

In order to explore the role of TGF-β1 in scleral remodeling and the possible mechanism,the influence of high level TGF-β1 on scleral thickness and the expression of MMP-2 and TIMP-2 was investigated in a TGF-β1 transgenic mouse model.Alb/TGF-β1(Cys223,225Ser) TGF-β1 transgenic mice were used as experimental subjects and non-transgenic littermates as controls.Plasma levels of TGF-β1 were determined by ELISA.TGF-β1,MMP-2 and TIMP-2 levels in sclera were detected by using Western blot.The thickness of posterior sclera was measured by computerized image analysis of a midsagittal section.Mean difference was analyzed with independent t-test.The results showed plasma levels of TGF-β1 in transgenic mice were 1.68 times as much as that in the controls(P<0.01).TGF-β1 levels in the sclera of transgenic mice were 2.68 times of the controls(P<0.01).Posterior scleral thickness in transgenic mice were significantly thicker than in the controls.There was no significant difference in the MMP-2 levels between transgenic mice and controls,but the TIMP-2 levels were increased significantly in transsgenic mice as compared with those in the controls.It was suggested that high levels of TGF-β1 in transgenic mice could result in the increased scleral thickness by inducing the expression of TIMP-2 to suppress the activity of MMP-2,finally inhibiting the degradation of collagen.     

Effect of TGF-β1 on the Expression of IL-12, IL-15, IL-18, IL-4 and IL-10 in Heart Transplantation Rejection in Rats

To investigate the effect of TGF-β1 on the expressions of IL-12, IL-15, IL-18, IL-4 and IL-10 in heart transplantation rejection in rats, a model of rat cervical heterotopic heart transplantation was set up and the model rats were randomly divided into three groups： control group, transplant group and TGF-β1 group. The mRNA expression levels of IL-12, IL-15, IL-18, IL-4 and IL-10 were determined by RT-PCR at the 5th day after the transplantation. The mRNA expression levels of IL- 12, IL-15, IL-18 were increased obviously and those of IL-4, IL-10 were significantly decreased in the transplant group as compared with the control group （P〈0.01）. In the TGF-β1 group, the mRNA ex- pression levels of IL- 12, IL- 15, IL- 18 were significantly decreased and those of IL-4, IL- 10 were significantly increased as compared with the transplant group （P〈0.01）. The immunosuppressive effect of TGF-β1 on heart transplantation rejection was related to its inhibition of the expressions of Th1-type cytokines （IL-12, IL-15, IL-18 etc） and its promotion of the expressions of Th2-tpye cyto- kines （IL-4, IL-10）.     

Regulation of the expression and function of glucose transporter-1 by TGF-β1 and high glucose in mesangial cells

Objective To study the effects of high glucose and transforming growth factor-β1 (TGF-β1) on the expression and function of glucose transporter-1 (GLUT1) in mouse mesangial cells.Methods Cultured mouse mesangial cells were used.The expression of GLUT1 mRNA was detected by Northern Blot; glucose uptake and its kinetics were determined with a 2-Deoxy-［(3)H］-D-glucose uptake assay.Results Mesangial cells exposed to enriched glucose medium (20 mmol/L) for 72 hours demonstrated a decrease in both GLUT1 mRNA and V(max) for uptake of the glucose analog, 2-deoxy-D-glucose　(2DOG), as compared to mesangial cells cultured in physiologic glucose concentrations(5.5 mmol/L).In contrast, hypertonic mannitol had no effect on GLUT1 mRNA levels.TGF-β1 treatment for 10 hours stimulated 2DOG uptake, both in 5.5 mmol/L and 20 mmol/L glucose medium, by approximately 4.28-fold in a dose-dependent manner (2 ng/ml maximum).Kinetic analysis of 2DOG uptake revealed an increase in V(max) and a decrease in K(m) in the presence of TGF-β1. TGF-β1 also up-regulated the expression of GLUT1 mRNA in mesangial cells.The addition of anti-TGF-β neutralizing antibody (30 μg/ml) in mesangial cells cultured in enriched glucose medium (20 mmol/L) led to a 40% decrease in 2DOG uptake.Conclusions The expression of GLUT1 can be suppressed by exposure of mesangial cells to high glucose medium, which may serve as a protective mechanism against possible adverse effects of excessive glucose flux into cells.TGF-β1 stimulates glucose uptake by enhancing the expression and function of GLUT1 in mesangial cells.This effect is independent of the glucose milieu in the cultured medium.     

Role of BMP-7 and TGF-β1 expression in renal tubulo-interstitial lesion of Wistar rats induced by unilateral ureteral obstruction

Objective： To explore the role of bone morphorgenetic protein-7 （BMP-7） in the renal tubulo-interstitial lesions induced by unilateral ureteral obstruction （UUO）. Methods： Sixty Wistar rats were equally and randomly divided into normal control, sham operation and UUO groups, and respectively sacrificed on the 1st, 3rd, 7th, 14th day after the time of UUO operation. The mRNA levels of BMP-7 and TGF-β1 in the renal tissues were examined by RT-PCR. The expression sites and levels of BMP-7 and TGF-β1 proteins were detected by immunohistochemistry staining. Results：Compared to control groups, the level of BMP-7 mRNA was significantly decreased, but that of TGF-β1 mRNA was significantly increased in UUO rats. Immunohistochemistry staining indicated that BMP-7 mainly expressed in the renal tubules and interstitum, rarely in the glomeruli. In UUO rats, the expression of BMP-7 protein was decreased, but that of TGF-β1 was increased in an obstruction dependent manner. Conclusion：The downregulation of BMP-7 is observed in the early phase of fibrotic process of the renal interstitium, suggesting it may be involved in the formation and development of the tubulo-interstitial lesions.     

Expression of TGF-β1 in Placenta of the Patients with Pregnancy-induced Hypertension and Its relationship with Serum VCAM-1

Pregnancy induced hypertension ( PIH) is asyndrome that remains the major cause of maternaland perinatal morbidity and mortality all over theworld. The pathogenesis of PIH is incompletelyunderstood. It is thought that vascular endothelialcell damage and dysfunction play an importantrole, and a lack of or an incomplete invasion oftrophoblasts into the maternal spiral arteries is thematerial feature in pathogenesis of PIH[1]. In thisstudy, in order to explore the…     

The Dynamic Change of TGF-β1 in the Myocardial Remodeling of Rat after Myocardial Infarction

Chronic heart failure is the leading cause of mortality and morbidity in most countries. Ventricular remodeling was the important pathophysiological process of heart failure. Mechanical overload, neurohormones and system nerve adrenal gland system can evoke remodeling. There are plentiful evidence indicating that inflammation plays an important role in the ischemic cardiac disease[1—3]. In this study we used the MI rat to observe the morpho- logical change of the ventricle, expression of the…     

Smad signal transduction pathway involved in supression of VEGF on TGF-β1 induced EMT of HK-2 cells

目的 探讨血管内皮生长因子(VEGF)抑制转化生长因子-β1(TGF-β1)诱导HK-2细胞发生肾小管上皮-间充质细胞转化(EMT)的过程中对Smad 2/3,Smad 7信号途径以及SnoN表达的影响.方法 体外培养的HK-2细胞分为:①正常对照组;②TGF-β1(5μgL)阳性对照组;③VEGF165(100μg/L)作用组;④TGF-β1(5 μg/L)+ VEGF165(100 μg/L)共同作用组.采用Western Blot法和RT-PCR分别检测各组细胞p-Smad 2/3和Smad 2/3(共同作用30和60 min),α-平滑肌肌动蛋白(α-SMA)、Smad 7 、SnoN的表达水平(共同作用48 h).结果 TGF-β1组α-SMA蛋白和mRNA表达与正常对照组比较明显增强,TGF-β1与VEGF165共同作用组α-SMA蛋白和mRNA表达与TGF -β1单独作用组比较明显减弱(P＜0.05).体外HK-2细胞,TGF-β1组刺激30、60 min,与正常对照组比较,(p-Smad 2/3)/(Smad 2/3)比值明显升高,TGF-β1 +VEGF165组与TGF-β1单独作用组相比明显下降,且以30 min时下降明显.TGF-β1组作用48h与正常对照组比较,Smad7蛋白和mRNA表达明显下降,VEGF165+TGF-β1组较TGF-β1单独作用组Smad 7表达明显升高(P＜0.05).VEGF165组与正常对照组相比,α-SMA、(p-Smad 2/3 )/(Smad 2/3)、Smad 7蛋白和mRNA表达的差异无统计学意义(P＞0.05).TGF-β1组SnoN蛋白表达与正常对照组比较明显增强(P＜0.05),TGF-β1与VEGF165共同作用组SnoN蛋白表达与TGF-β1单独作用组相比差异无统计学意义(P＞0.05),各组SnoN mRNA表达差异均无统计学意义(P＞0.05).结论 VEGF165抑制TGF-β1诱导HK-2细胞EMT的机制可能与直接抑制Smad 2/3磷酸化、上调Smad 7信号表达有关,而与调节SnoN表达无关.     

IL-5 Up-regulates the Expression of TGF-β1 in Human Blood Eosinophils in Vitro

Withthedevelopmentofimmunosuppressivetherapy,therateofacuterejectioninhomotrans plantationhasdecreasedsubstantiallyinclinicalpractice.Therateoflosinggraft,however,hasincreasedatarateof3%-5%eachyear.There fore,howtoimprovethesurvivalratehasbecomeamatterofurgency.Eosinophilsareoneoftheef fectorcellsintherejectionoftransplantation.TheyareactivatedandaccumulatedbyarangeofTcell derivedcytokines.Amongthese,IL5,whichissecretedbyasubsetofhelperTcells(Th2),ismoreimportanteffective[1].Afterthetranspl…     

TGF-β1及其受体mRNA在哮喘大鼠肺组织中的表达

目的研究哮喘大鼠肺组织中TGF-β1及受体TGF-βRⅠ、TGF-β RⅡmRNA的表达水平,以了解TGF-β1在哮喘中的作用及其受体对其作用的调节机制.方法将30只成年雌性SD大鼠分为正常对照组,单纯致敏组和哮喘模型组,采用卵清蛋白(OVA)腹腔注射法复制大鼠哮喘模型,利用RT-PCR法检测肺组织中TGF-β1、TGF-βRⅠ及TGF-βRⅡmRNA的表达水平.结果TGF-β1mRNA的表达水平致敏组与正常组相比增加(70.21±11.68 vs 53.07±10.27,P＜0.05),哮喘组与正常组相比显著增加(114.14±16.57 vs 53.07±10.27,P＜0.01),TGF-β R Ⅰ mRNA的表达水平在致敏组和哮喘组相当,均较正常组下调(83.21±11.52 vs 100.14±16.13,85.76±12.95 vs 100.14±16.13,P＜0.05).TGF-βRⅡmRNA的表达水平致敏组与正常组相比有下降(89.04±9.23 vs 103.05±11.46,P＜0.05),哮喘组与正常组相比则显著下降(56.53±7.34 vs 103.05±11.46,P＜0.01).结论TGF-β1可能作为一个抗炎因子在哮喘的变应性炎症前阶段及炎症过程中起着重要作用,TGF-β RⅠ、TGF-β RⅡ的表达水平在哮喘组和致敏组的下降说明TGF-β1信号通路在哮喘的变应性炎症中和炎症前阶段的活化程度,TGF-βRⅡ表达水平在哮喘组的显著下降则显示TGF-β1信号通路可能被下调从而抑制其抗炎作用的发挥.     

TGF-β1在胃癌中的表达

目的研究TGF-β1在胃癌发生、发展过程中的作用。方法采用免疫组织化学Envision二步法对68例胃癌及30例正常胃黏膜组织的TGF-β1进行检测,分析对比检测结果。结果 TGF-β1胃癌组织中表达明显高于正常胃组织,两者之间比较具有显著性差异（P〈0.05）。结论 TGF-β1的表达与癌细胞分化程度、浸润程度以及淋巴结转移有关,TGF-β1的表达检测对胃癌的早期诊断与判断预后有重要意义。     

子痫前期患者血浆uPA、TGF-β1含量变化及意义

目的 探讨子痫前期患者血浆尿激酶型纤溶酶原激活因子(uPA)和转化生长因子β1(TGF-β1)含量的变化及其在子痫前期发病中的意义.方法 采用酶联免疫吸附法测定70例子痫前期患者(子痫前期组,其中轻度患者30例,重度患者40例)和40例正常晚孕妇女(对照组)血浆uPA和TGF-β1含量.结果 ①正常晚孕组血浆uPA含量为(646.54±35.39)pg/mL,子痫前期组为(436.39±29.57)pg/mL,两组比较差异有统计学意义(P＜0.01);轻度子痫前期组为(468.81±14.91)pg/mL、重度子痫前期组为(417.11±48.47)pg/mL,均低于正常晚孕组(P均＜0.01);轻、重度组之间比较差异无统计学意义(P＞0.05);②正常晚孕组血浆TGF-β1含量为(9.85±3.19)ng/mL,子痫前期组为(14.32±4.37)ng/mL,两组比较差异有统计学意义(P＜0.05);轻度子痫前期组为(11.21±2.32)ng/mL、重度子痫前期组为(15.37±4.93)ng/mL,均高于正常晚孕组(P均＜0.05);轻、重度组之间比较差异无统计学意义(P＞0.05).③子痫前期患者血浆uPA和TGF-β1含量呈负相关(r=-0.497,P＜0.01).结论 子痫前期患者血浆uPA水平下降、TGF-β1水平升高与子痫前期发病及其严重程度有关.     

The effects of genistein on TGF-β1-induced the invasion and metastasis in human pancreatic cancer cell line Panc-1

Pancreatic cancer is a devastating disease with the worst mortality rate. Therefore, a rational strategy for future drug development is critical. Genistein is a small, biologically active flavonoid that is found in high amounts in soy. This important compound possesses a wide variety of biological activities, but it is best known for its ability to inhibit cancer progression. In the current study, we found that genistein can inhibit effectively TGF-β1-induced the invasion and metastasis in Panc-1 by Transwell assay, which is through regulating the mRNA and protein expression of uPA and MMP2, but not MMP9 by RT-PCR / Weston blot, and is positively correlated with the concentration of genistein. At the same time, genistein also could improve the progress of Epithelial-Mesenchymal Transition (EMT) via morphology observation using light microscope / TEM, which is mediated by the down-regulation of E-cadherin and the up-regulation of vimentin. TGF-β1 mediates EMT process via numerous intracellular signal transduction pathways. The potential molecular mechanisms are all or partly through Smad4-dependent and -independent pathways (p38 MAPK) to regulate the antitumor effect of genistein.     

人乳癌组织中TGF-β1的表达

目的：探讨人乳癌组织中TGF-β1的表达与临床病理分期的关系。方法：应用免疫组织化学S-P法检测不同乳腺组织（导管原位癌12例;浸润性乳癌50例,包括髓样癌5例,黏液癌4例,浸润性导管癌41例;正常乳腺组织15例）中TGF-β1的表达（癌组织按TNM分期,0～Ⅰ期17例,Ⅱ～Ⅲ期45例）。结果：正常乳腺和乳癌组织中TGF-β1的表达差异有统计学意义（P=0．041）;在0～Ⅰ期与Ⅱ～Ⅲ期乳癌组织之间及有腋淋巴结转移和无腋淋巴结转移组织之间差异也有统计学意义（P分别为0．026,0．018）;但在不同组织学分级乳癌组织间其表达差异无统计学意义（P=0．538）。结论：TGF-β1有助于判断乳癌患者的临床病理分期并对腋淋巴结有无微转移灶做出评估,进而指导外科治疗。     

Differential BMP-1 expression in injured anterior cruciate ligament and medial collateral ligament fibroblasts induced by TGF-β1

目的 观察在转化生长因子-β1(transforming growth factor betal,TGF-β1)作用下,损伤的前交叉韧带(anterior cruciate ligament,ACL)和内侧副韧带(medial collateral ligament,MCL)中骨形态发生蛋白-1(bone morphogenetic protein-1,BMP-1)基因的表达,找出TGF-31、BMP-1之间的关系,揭示机械损伤后ACL和MCL细胞中BMP-1的表达差异.方法 采用反转录PCR(RT-PCR)和实时荧光定量PCR方法检测1、5、50 ng/ml TGF-β1处理后2h受损的ACL和MCL细胞中BMP-1的表达以及5 ng/ml TGF-β1作用2、6、12、24h受损的ACL和MCL细胞中BMP-1的表达;Western blot检测5 ng/mlTGF-β1处理48 h后受损的ACL和MCL细胞中BMP-1的表达.结果 受损的ACL和MCL细胞中BMP-1的基因表达比正常状态下偏高,并随着TGF-β1浓度的增大而增高,在MCL中的增高程度比在ACL中高出近1倍(P＜0.05);与正常组相比,在5 ng/ml TGF-β1处理24h后,ACL细胞中BMP-1的表达在24h达到最高比例(约为6.1倍),而在MCL中12h达到最高比例(约为9.84倍,P＜0.05).5 ng/ml TGF-β1处理48 h后BMP-1蛋白也明显上调,与无TGF-β1处理的对照组相比,ACL细胞中BMP-1上调2.32倍,MCL细胞中BMP-1上调3.84倍(P＜0.05).结论 TGF-β1刺激BMP-1的变化可能直接影响到细胞外基质中活性赖氨酰氧化酶的表达,对损伤ACL和MCL的修复有极其重要的参考价值和临床意义.     

脑挫裂伤后TGF-β1及其受体TβRI的表达

目的：观察人脑损伤后TGF-β1及其受体TβRI蛋白的表达，探讨脑挫裂伤的分子机制及其受体TβRI在脑挫裂伤中的作用。方法：用免疫组织化学方法观察60例脑挫裂伤手术标本中TGF-β1及其受体TβRI的表达，以非脑损伤死亡尸脑组织作为对照。结果与结论：脑挫裂伤可诱导TGF-β1及其受体的表达，表达TGF-β1以巨噬细胞，小神经胶质细胞为主；表达TβRI以神经元为主，其次是胶质细胞。     

转化生长因子β1（TGF-β1）在胃癌组织中的表达

目的检测转化生长因子β1（transforming growth factor beta 1,TGF-β1）在胃癌组织及其相应正常胃黏膜组织中的表达,并分析其与胃癌患者临床病理学特征之间的关系。方法选取39例经外科手术切除及组织病理学证实的胃癌患者的癌组织标本及相应的正常胃黏膜组织,应用RT-PCR技术和冰冻切片免疫组化染色方法,分别在mRNA和蛋白水平检测TGF-β1的表达。结果30例胃癌组织有TGF-β1的阳性表达。在临床Ⅰ期和Ⅱ、Ⅲ、Ⅳ期两组以及浸润深度为T1和T2、T3、T4两组胃癌患者的癌组织中TGF-β1阳性表达差异有统计学意义（P〈0.05）。胃印戒细胞癌胞浆频繁出现TGF-β1强阳性染色。结论TGF-β1在胃癌发生、发展中发挥着重要作用,TGF-β1可成为早期胃癌诊断、治疗和预后的分子标志。