胸腺肽Tβ4

胸腺肽Tβ4是具有多重生物功能的小肽,是肌动蛋白的结合蛋白之一,该多肽的基因差异性表达与肿瘤恶变和转移、胚胎发育等关系密切,本综述了胸腺肽Tβ4的研究进展。     

RanBPM interacts with TβRI,TRAF6 and curbs TGF induced nuclear accumulation of TβRI

Transforming growth factor β (TGF-β), a cytokine, and its receptors play a vital role during normal embryogenesis, cell proliferation, differentiation, apoptosis and migration. Ran-binding protein in the microtubule-organizing center (RanBPM) serves as a scaffold protein that has been shown to interact with many other proteins, such as MET, Axl/Sky, TRAF6, IFNR, TrKA and TrkB in addition to p75NTR. In the current study, we have identified RanBPM as a novel binding partner of TβRI by yeast two-hybrid assay. The TβRI and RanBPM association was confirmed by co-immunoprecipitation and GST pull-down experiments. Additionally, expression of RanBPM abrogated the interaction between TβRI and TRAF6. Furthermore, RanBPM could depress TGF-β induced TRAF6 ubiquitination, subsequent NF-κB signaling pathway, and block TGF-β induced TβRI nuclear accumulation. Taken together, our results reveal that RanBPM may modulate TGF-β-mediated downstream signaling and biological functions.     

β-Glucuronidase activity in human T and B lymphocytes and the Tμ and Tγ subpopulations

Summary The -glucuronidase staining characteristics of isolated T cell populations and the T and T enriched fractions derived of them were studied. T lymphocytes were obtained from purified T lymphocytes by ox-IgG rosette sedimentation. The rosette-forming cells in the pellet were referred to as T lymphocytes, whereas the lymphocytes in the interface were referred to as T depleted or T lymphocytes. B cells were studied on rosetted mononuclear cells with either mouse erythrocytes or with Staphylococcus Aureus (Cowan I) bacteria, after a preceeding polyvalent anti-human Ig treatment of the cells. While B cells showed mostly no reactivity, T and T cells were respectively characterised by a dot-like and granular pattern of reactivity. These findings are in agreement with those observed by others after -naphthyl-acetate esterase or acid phosphatase staining. Within the T lymphocyte fraction, the T non-, non lymphocytes seemed to have a granular pattern of reactivity. The same staining pattern was found in non-B, non-T lymphocytes.     

Clinical Implications of TβRII Expression in Breast Cancer

Objective

To explore the relationship between TβRII [type II TGFβ (transforming growth factor β) receptor] expression and clinicopathological characteristics, and to evaluate the prognostic significance of TβRII expression in breast cancer.

Methods

Clinicopathological data and prognostic information of 108 patients with histologically confirmed breast cancer who were surgically treated at China Medical University between January 2007 and September 2008 were reviewed and the association between the clinicopathological characteristics and TβRII expression was analyzed by chi-square test and multivariate analysis. The expression of TβRII was assessed by immunohistochemistry.

Results

Of the 108 patients, 60 cases were TβRII positive and 48 cases were negative. There was no significant association between TβRII expression of the patients older than 40 years and that of the younger than 40 years (56.0% vs 50.0%; P = 0.742). The TβRII expression rate was significantly increased in patients with lymph node metastasis compared to those without lymph node metastasis (67.40% vs 46.8%; P = 0.033). Statistically significant relationships were found between increasing tumor clinical stage and high TβRII expression (P = 0.011). TβRII expression was not associated with the expression of ER(estrogen receptor)、PR, (progesterone receptor)、Her-2 (human epidermal growth factor receptor 2) (P = 0.925,P = 0.861, and P = 0.840, respectively). Patients with high TβRII expression showed poorer 5-year disease-free survival (DFS) compared to those with low expression (66.7% vs 45.6%; P = 0.028) by univariate analysis. Survival analysis demonstrated that TβRII was associated with poor DFS (P = 0.011). Subgroup analysis revealed that TβRII expression was associated with shorter DFS in patients with lymph node metastasis, ER-positive, PR-positive or Her-2-negative tumors (P = 0.006, P = 0.016, P = 0.022, and P = 0.033, respectively). Cox regression analysis revealed that high TβRII expression was related to poor 5-year DFS, and it was an independent factor for predicting the poor outcome for breast cancer patients (P = 0.016).

Conclusions

High levels of TβRII expression were associated with lymph node metastasis, increasing tumor clinical stage, and poorer 5-year DFS in patients with breast cancer. TβRII may be a potential prognostic marker for breast cancer.     

在活细胞中应用FRET技术研究TGFβ/TβRI信号传导

转移生长因子β(TGFβ)信号传导通路参与调节细胞的增殖、分化、凋亡、细胞迁移等一系列细胞过程,与骨代谢疾病的发病机制密切相关.本研究根据荧光共振能量转移(FRET)技术原理,构建包含CFP-TβRI-YFP融合蛋白的TβRI生物传感器,转染293T细胞,观察转染效率.以TGFβ1为诱导剂,激活TGFβ/TβRI信号传导通路,在活细胞生理条件下,动态监测TβRI生物传感器的FRET效应.结果表明,成功构建了TβRI生物传感器,转染细胞效率达50%,在TGFβ1诱导刺激6min后,FRET效率增加并达到最大值,该过程经历9 min后,随时间的延长,FRET效率下降.研究结果表明:在活细胞生理条件下,TGFβ1/TβRI信号转导过程存在一定的时间特异性.     

子宫内膜癌中TGF-β1及受体TβRI的表达及其临床意义

目的：研究转化生长因子（TGF-β1）及其Ⅰ型受体（TβRI）在子宫内膜癌组织中的表达及其临床意义。方法：采用RT-PCR方法检测36例子宫内膜癌及31例正常子宫内膜组织中TGF-β1及TβRI基因的表达水平,分析其与临床病理参数之间的关系。结果：子宫内膜癌组织中TGF-β1mRNA的表达明显高于正常组织（P〈0.05）,而TβRI mRNA的表达水平明显低于正常内膜组织（P〈0.05）。TGF-β1mRNA及TβRImRNA在子宫内膜癌中的表达均与肿瘤的临床分期、组织学分级、肌层浸润深度、淋巴结转移呈显著性相关（P〈0.05）,差别有统计学意义。结论：TGF-β1及其Ⅰ型受体TβRI在子宫内膜癌的发生、发展中可能起重要作用,检测TGF-β1及TβRI对评价子宫内膜癌的转移及预后有重要价值。     

Interaction of TGFβ3 ligand with its receptors type II (TβRII) and type I (TβRI): A unique mechanism of protein-protein association

The proper orchestration of transforming growth factor beta (TGFβ) mediated signal transduction depends upon a delicate set of interactions between specific ligands and their receptors. Here we present an in-depth profiling of the binding mechanism of TGFβ3 ligand with its type II and type I receptors (TβRII and TβRI) using isothermal titration calorimetry (ITC). Studies were carried out in acidic pH as it has great physiological relevance for TGFβ3 activity. Our findings reveal an unusual positive enthalpy (∆H) compensated by a large favourable entropy (∆S) during TGFβ3-TβRII interaction. In addition to the hydrophobic effect, we propose that a distinct conformational switch from “closed” to “open” form as experienced by TGFβ3 on binding to TβRII is contributing significantly to the increase in overall entropy of the system. Binding studies of TGFβ3 and TβRII were carried out at different pH values and salt concentrations to gain further insight into the thermodynamics of the interaction. Furthermore, the importance of hydrophobic interactions on the binding affinity of TβRII with TGFβ3 was confirmed by two TβRII variants (interfacial). Finally, a distinct shift from entropy to enthalpy dominated interaction was observed upon recruitment of TβRI to the binary complex forming the ternary complex.     

子宫内膜癌中TGF-β_1及受体TβRI的表达及其临床意义

目的:研究转化生长因子(TGF-β_1)及其Ⅰ型受体(TβRI)在子宫内膜癌组织中的表达及其临床意义。方法:采用RT-PCR方法检测36例子宫内膜癌及31例正常子宫内膜组织中TGF-β_1及TβRI基因的表达水平,分析其与临床病理参数之间的关系。结果:子宫内膜癌组织中TGF-β_1mRNA的表达明显高于正常组织(P<0.05),而TβRI mRNA的表达水平明显低于正常内膜组织(P<0.05)。TGF-β_1mRNA及TβRImRNA在子宫内膜癌中的表达均与肿瘤的临床分期、组织学分级、肌层浸润深度、淋巴结转移呈显著性相关(P<0.05),差别有统计学意义。结论:TGF-β_1及其Ⅰ型受体TβRI在子宫内膜癌的发生、发展中可能起重要作用,检测TGF-β_1及TβRI对评价子宫内膜癌的转移及预后有重要价值。     

Mutual regulation of TGF-β1, TβRII and ErbB receptors expression in human thyroid carcinomas

The role of EGF and TGF-β1 in thyroid cancer is still not clearly defined. TGF-β1 inhibited the cellular growth and migration of follicular (FTC-133) and papillary (B-CPAP) thyroid carcinoma cell lines. Co-treatments of TGF-β1 and EGF inhibited proliferation in both cell lines, but displayed opposite effect on their migratory capability, leading to inhibition in B-CPAP and promotion in FTC-133 cells, by a MAPK-dependent mechanism. TGF-β1, TβRII and EGFR expressions were evaluated in benign and malignant thyroid tumors. Both positivity (51.7% and 60.0% and 80.0% in FA and PTC and FTC) and overexpression (60.0%, 77.7% and 75.0% in FA, PTC and FTC) of EGFR mRNA correlates with the aggressive tumor behavior. The moderate overexpression of TGF-β1 and TβRII mRNA in PTC tissues (61.5% and 62.5%, respectively), counteracted their high overexpression in FTC tissues (100% and 100%, respectively), while EGFR overexpression was similar in both carcinomas. Papillary carcinomas were positive to E-cadherin expression, while the follicular carcinomas lose E-cadherin staining. Our findings of TGF-β1/TβRII and EGFR overexpressions together with a loss of E-cadherin observed in human follicular thyroid carcinomas, and of increased migration ability MAPK-dependent after EGF/TGF-β1 treatments in the follicular thyroid carcinoma cell line, reinforced the hypothesis of a cross-talk between EGF and TGF-β1 systems in follicular thyroid carcinomas phenotype.     

骨骼肌特异性敲除TβRⅡ小鼠模型的建立

目的:建立骨骼肌特异性敲除转化生长因子受体Ⅱ(TβRⅡ)小鼠模型,为进一步研究TβRⅡ在骨骼肌发育和分化中的作用奠定基础。方法:首先将TβRⅡflox/flox转基因小鼠与上游携带肌酸激酶(MCK)启动子的MCK-Cre转基因小鼠进行杂交,培育繁殖出TβRⅡflox/wt/MCK-Cre(+)双转基因小鼠。然后利用TβRⅡflox/wt/MCK-Cre(+)双转基因小鼠与TβRⅡflox/flox转基因小鼠进行杂交,繁殖培育出在骨骼肌内特异敲除TβRⅡ基因的TβRⅡflox/flox/MCK-Cre(+)小鼠。结果:利用Cre/loxP技术世界上首次成功繁殖培育出有活力的且发育正常的TβRⅡ基因敲除小鼠。     

Surfactant protein A modulates induction of regulatory T cells via TGF-β

TCR signaling plays a critical role in regulatory T cell (Treg) development. However, the mechanism for tissue-specific induction of Tregs in the periphery remains unclear. We observed that surfactant protein A (SP-A)-deficient mice have impaired expression of Foxp3 and fewer CD25(+)Foxp3(+) Tregs after ex vivo stimulation and after stimulation with LPS in vivo. The addition of exogenous SP-A completely reversed this phenotype. Although SP-A is known to inhibit T cell proliferation under certain activation conditions, both IL-2 levels as well as active TGF-β levels increase on extended culture with exogenous SP-A, providing a key mechanism for the maintenance and induction of Tregs. In addition, kinetic suppression assays demonstrate that SP-A enhances the frequency of functional Foxp3(+) Tregs in responder T cell populations in a TGF-β-dependent manner. In mice treated with LPS in vivo, Tregs increased ～160% in wild-type mice compared with only a 50% increase in LPS-treated SP-A(-/-) mice 8 d after exposure. Taken together, these findings support the hypothesis that SP-A affects T cell immune function by the induction of Tregs during activation.     

Antigen-specific TGF-β-induced regulatory T cells secrete chemokines, regulate T cell trafficking, and suppress ongoing autoimmunity

The ability to regulate ongoing inflammation using regulatory T cells (Tregs) is under intense investigation. Strategies to induce and expand Ag-specific Tregs are being developed, and whether various types of Tregs are suppressive in the inflammatory conditions associated with ongoing disease needs to be determined. In this study, we report that TGF-β-induced Tregs (iTregs) and expanded Tregs specific for a major self-Ag in autoimmune gastritis suppress inflammation and associated pathology when administered late in the process of ongoing disease. Transferred iTregs localized to the stomach, maintained Foxp3 and suppressor functions, and engaged several distinct mechanisms to alleviate disease progression. In addition to suppressing the production of inflammatory cytokines in the stomach and preventing the destruction of parietal cells, we show that iTregs secrete numerous chemokines and regulate both iTreg and effector T cell trafficking into the stomach. These data support efforts to use iTregs in therapies to treat autoimmunity and inflammatory diseases and provide novel insight into the biological mechanisms of iTreg-mediated immune suppression.     

产β-葡聚糖酶菌种T199的选育及发酵条件

A mutant strain T199 producing about 8 times as much β-glucanase as its parent strain trichoderma kningii T3 was obtained by treatment with ultraviolet light and N-methyl-N-nitro-N-nitrosoguanidine.Fermentation was conducted in 250mL flask,each containing 30mL of medium consisted of 5% corn cob powder,3% wheat bran and 1.4% nitrogen source No.10 ((NH 4) 2SO 4 10%,Peptone 20%,Yeast extract 15%).The optima culture conditions were as below:initial pH5.0,30℃,shaking speed 280r/min,and cultivation time 5d.En…     

Integrin α4β7 Co-Stimulation of Human Peripheral Blood T Cell Proliferation

The Integrin α4β7 mediates lymphocyte adhesion to VCAM-1 on activated endothelium, fibronectin in the extracellular matrix, and the mucosal vascular addressin MAdCAM-1. It is unclear whether α4β7 performs any function beyond directing specific adhesion reactions. We addressed the possibility that triggering of α4β7 with a specific monoclonal antibody was capable of delivering an accessory stimulus that would coactivate T cells and lead to proliferation. At submitogenic levels of anti-CD3 stimulation, triggering of α4β7 by immobilized mAb ACT-1 resulted in T cell blastogenesis, IL-2 production, expression of the IL-2 receptor α chain CD25, and ultimately DNA synthesis. These results indicate that the integrin α4β7 is involved in more than lymphocyte adhesion and homing but also plays a role in cell signaling.     

5例前列腺癌T细胞受体β链CDR3的多样性分析

T淋巴细胞受体(TCRs)在抗原识别免疫应答中作用重要,其多样性与宿主免疫反应及肿瘤预后判断密切相关。目的:采用高通量测序技术研究前列腺癌组织和癌旁组织中T细胞受体(TCR)克隆多样性及其克隆序列。方法:收集5例PC患者的癌组织和癌旁组织,提取DNA后经多重PCR技术对TCRβ链CDR3区进行扩增。用Illumina MiSeq进行测序,经过数据处理和比对分析,比较前列腺癌组织TCR CDR3组库的组成特征。结果:前列腺癌组织具有更高程度的克隆百分比和较高的高度扩增克隆比HEC(HEC:频率样本总读数的0. 5%的TCR克隆),并获得了24对在癌组织样本中差异表达的V-J基因组合、16对在癌旁组织样本中差异表达的V-J基因组合。结论:前列腺癌组织与癌旁组织均存在差异性的V-J基因组合以及高克隆表达的HEC,其中癌组织样品具有更高的HEC。PC发生发展对免疫学研究提供了新的数据,对PC免疫监视、T细胞受体变异标志等研究提供了参考,对以后继续研究打下了基础。     

人类T细胞受体Vβ12基因编码区的等位多态性

T细胞抗原受体(TCR)β基因可变区核苷酸序列的变异,将影响到T细胞识别外来抗原的特异性。本文使用单链构象多态性(SSCP)技术,研究了TCRVβ12基因编码区的等位变异作用。在227例个体中,检出4个等位基因。它们按孟德尔定律分离和传递。在群体中的频率分别为0.4722、0.3166、0.2056和0.0056。核苷酸顺序分析表明存在1—3个核苷酸取代。但均为无声取代(Silent substitution),即氨基酸的顺序未改变。结果提示TCR Vβ12的蛋白质结构是高度保守的。     

产β—葡聚糖酶菌种T199的选育及发酵条件

大麦为啤酒酿造原料 ,含有由葡萄糖残基通过β 1 ,3 和 1 ,4 糖甙键连接而成的β 葡聚糖。在麦芽汁制备过程中 ,热不稳定的大麦葡聚糖酶不能充分降解β 葡聚糖 ,残留的 β 葡聚糖不仅影响麦芽汁分离和啤酒过滤 ,而且将成为成品啤酒出现混浊和沉淀的因素之一。微生物 β 葡聚糖酶能改善啤酒加工工艺和提高产品质量[1,2 ] 。谷类饲料含有不同于纤维素的 β 葡聚糖[2 ] ,作为抗营养因子 ,β 葡聚糖使饲料具有粘性 ,不能很好的消化利用。β 葡聚糖酶作为饲料添加剂加入到饲料中 ,可以将 β 葡聚糖降解 ,从而提高饲料利用率 ,改善营养吸收。相关…