转化生长因子βⅡ型受体在小鼠肾发育中的表达

目的:观察转化生长因子βⅡ型受体(TβRⅡ)在小鼠肾发育中的时空性表达,探讨转化生长因子β(TGF-β)与肾发育的关系。方法:采用免疫组织化学法、体视学和免疫印迹法测定不同胚龄(E)12、14、16和18d及生后日龄(P)1、3、7、14、21、28和42d小鼠肾内TβRⅡ的表达及其含量变化。结果:免疫组织化学结果显示TβRⅡ在各期肾小体、肾小管及集合管内均有表达,但在各期近端小管强烈表达,各期集合管表达较强,而各期肾小体、远端小管内表达较弱。体视学测量结果显示TβRⅡ在各期肾小体、肾小管及集合管的表达量均逐渐增加。免疫印迹结果显示TGF-βRⅡ随着肾的发育其表达量逐渐增加。结论:TGF-β可能对肾各结构的发育以及成熟肾各结构的维持起重要作用,尤其在近端小管的发育方面作用更为显著。     

转化生长因子βⅡ型受体与纤维连接蛋白在小鼠肾发育中的表达

目的 观察转化生长因子βⅡ型受体（TGF-βRⅡ）及纤维连接蛋白(Fn)在小鼠肾发育中的时空性表达,探讨TGF-βRⅡ和Fn与肾发育的关系。 方法 采用免疫组织化学技术,结合免疫印迹法,检测不同胚龄及生后日龄小鼠肾组织TGF-βRⅡ和Fn的表达及其含量变化。 结果 TGF-βRⅡ在各期肾小体、肾小管及集合管内均有表达,并随肾的发育其表达量逐渐增加(P ﹤0.05);Fn在除逗号小体以外的各期肾小体、肾小管及集合管的基底膜处均有表达,随着肾的发育其表达量逐渐增加(P ﹤0.05)。 结论 TGF-β和Fn可能对小鼠肾发育以及成熟肾脏各结构的维持起重要作用。     

伴有微卫星不稳定性的散发性结直肠癌转化生长因子-betaⅡ型受体基因突变的研究

目的:为了探讨在散发性结直肠癌的发生过程中转化生长因子βⅡ型受体基因(RII)的突变与微卫星不稳定性(RER)间的关系。方法: 我们应用PCR-SSCP-银染方法检测了50例散发性结直肠癌中的RER状态及RII基因突变情况(近端结肠19例,远端31例)。结果: RER+的共有13例(8例在近端,5例在远端),RII基因突变的共有5例。所有5例RII基因突变者均同时伴有RER+,而所有RER-病例均无RII基因突变。其中4例RII基因突变者位于回盲部肿瘤中。结论: 这些数据提示在散发性结直肠癌中,尤其是在回盲部肿瘤中,TGF-β RII基因的A₁₀重复序列是微卫星不稳定性的靶点,在肿瘤形成过程中可能起重要作用。     

转化生长因子β受体的研究进展

转化生长因子β受体有3个亚型;Ⅰ型、Ⅱ型、Ⅲ型,其结构功能特点及在转导TGF-β信号过程中的作用机制不同,细胞在受体水平的变化影响TGF-β的功能。     

转化生长因子α，β在人结、直肠癌、癌旁及正常肠粘膜组织中mRNA表达及其基因变化的分析

转化生长因子α，β（ＴＧＦ－α，β）分别作为正负自分泌生长调控因子，其在结、直肠癌的发生和发展过程中具有重要作用。本研究采用Ｄｏｔ，Ｎｏｒｔｈｅｒｎ及Ｓｏｕｔｈｅｒｎ杂交等分子生物学方法，探讨了１２例人结、直肠癌组织、癌旁及正常肠粘膜组织中ＴＧＦ－α，βｍＲＮＡ表达程度及其基因变化。研究发现，ＴＧＦ－αｍＲＮＡ的表达由高到低依次为癌、癌旁及正常肠粘膜组织，但癌组织及癌旁肠粘膜组织间无显著差异（Ｐ＞０．０５）。另外，发现１例病人的癌旁组织ＴＧＦ－αｍＲＮＡ的表达明显升高，且高于其相应的癌组织。ＴＧＦ－βｍＲＮＡ表达由高到低的顺序与ＴＧＦ－αｍＲＮＡ相反，为正常肠粘膜组织、癌旁肠粘膜组织和癌组织，前两者间无显著差异（Ｐ＞０．０５），而其与癌组织间均有显著性差异（Ｐ＜０．０５）。其中有２例病人的癌旁组织中，ＴＧＦ－βｍＲＮＡ表达高于其相应的正常组织。研究还发现，ＴＧＦ－αｍＲＮＡ表达可能与其基因扩增有关，而引起ＴＧＦ－βｍＲＮＡ表达变化的机制尚不清楚。上述研究结果初步表明：人结、直肠癌组织中ＴＧＦ－αｍＲＮＡ表达的增加和ＴＧＦ－βｍＲＮＡ表达的降低，可能通过自分泌和旁分泌生长调控作用同结、直肠癌的发生和进展有密切     

人结直肠癌组织中表皮生长因子受体1与Fascin-1蛋白表达的相关性及其临床意义

目的 探讨人结直肠癌组织中表皮生长因子受体1(EGFR)与Fascin-1蛋白表达的关系及其临床意义。方法 回顾性收集2008年1月-2010年12月东阳市人民医院病理科结直肠癌石蜡标本258例和同时切除的正常结直肠组织石蜡标本72例。采用免疫组织化学EnVision法检测并比较直肠癌组织和正常结直肠组织中EGFR和Fascin-1蛋白的表达;分析结直肠癌中Fascin-1蛋白表达与结直肠癌患者临床病理特征、EGFR的关系,以及EGFR和Fascin-1蛋白的表达与患者的预后生存情况的关系。结果 (1)结直肠癌组织中Fascin-1蛋白的阳性率为38.0%(98/258),高于正常结直肠组织的阳性率0.0%(0/72),差异有统计学意义(χ²=38.901,P＜0.01)。(2)女性、结肠及低分化的结直肠癌患者中Fascin-1蛋白的阳性率高于男性、直肠及高-中分化患者(χ²=4.256、20.085、8.471,P值均＜0.05)。(3)在EGFR阳性结直肠癌患者的Fascin-1蛋白阳性表达率(42.9%,91/212)较EGFR阴性病例(15.2%,7/46)高,差异有统计学意义(χ²=12.318, P＜0.01);Spearman相关分析显示,结直肠癌组织中EGFR和Fascin-1蛋白表达呈正相关(r_s=0.219,P＜0.01)。(4)194例获得随访的结直肠癌患者5年总生存率为73.2%(142/194),5年无复发生存率为65.5%(127/194)。其中EGFR和Fascin-1均阳性患者的5年平均总生存期及5年总生存率(47.8个月、64.7%)低于非均阳性患者(54.4个月、77.8%),差异有统计学意义(χ²=5.039, P＜0.05)。结论 结直肠癌中EGFR与Fascin-1蛋白的表达呈正相关,二者同时表达与患者预后不良有关。     

转化生长因子βⅠ型受体对组织纤维化形成及发展的影响

目的探讨转化生长因子βⅠ型受体(TGFβR-Ⅰ)对组织纤维化的形成及发展的影响。方法采用RNA干扰技术阻断人成纤维细胞系HFL-Ⅰ细胞的TGFβR-Ⅰ表达,Western blot法检测RNA干扰前后TGFβR-Ⅰ的表达水平,MTT法分析干扰前后的细胞生长状态,采用动物模型结合HE染色观察RNA干扰阻断TGFβR-Ⅰ表达前后的中毒性肝纤维化模型大鼠的肝脏病理学变化。结果特异性TGFβR-Ⅰ干扰RNA能有效抑制TGFβR-Ⅰ蛋白质合成和成纤维细胞株HFL-Ⅰ细胞的生长,正常鼠肝组织处于纤维化S0期,中毒性肝纤维化模型鼠肝组织处于纤维化S2期,特异性TGFβR-Ⅰ干扰RNA治疗组模型鼠肝组织则呈现纤维化S1期特征。结论抑制TGFβR-Ⅰ的表达可明显减轻中毒性肝纤维化模型大鼠的肝纤维化程度,对进一步优化肝纤维化的预防和治疗策略具有重要意义。     

转化生长因子β及其受体与胃癌的研究进展

ＴＧＦβ在胃癌组织及胃癌患者血浆中水平升高显著，它促进胃癌间质中胶原形成，与胃癌的不同病理分型有关；可促进胃癌间质中血管生成，抑制机体免疫能力，从而影响胃癌的转移。ＴＧＦβⅡ型受体基因在胃癌中的突变及ＴＧＦβ型受体表达水平下降，使胃癌细胞对ＴＧＦβ的敏感性下降，从而逃避ＴＧＦβ的增殖抑制、诱导凋亡作用，而呈恶性增殖。     

体外阻断卵巢颗粒细胞转化生长因子β信号转导通路模型的建立

本实验以选取转化生长因子βⅡ受体（transforming growth factor-βreceptor typeⅡ,TGF-βRⅡ)抗体的不同剂量和不同孵育时间,对原代培养的大鼠卵巢颗粒细胞表面TGF-βRⅡ进行中和,从而达到建立体外阻断TGF-β信号转导通路模型的目的.为研究与TGF-β信号转导通路相关的各种调节因素提供了体外研究的新模型.     

Transforming growth factor beta signaling: The master sculptor of fingers

Transforming growth factor beta (TGFβ) constitutes a large and evolutionarily conserved superfamily of secreted factors that play essential roles in embryonic development, cancer, tissue regeneration, and human degenerative pathology. Studies of this signaling cascade in the regulation of cellular and tissue changes in the three-dimensional context of a developing embryo have notably advanced in the understanding of the action mechanism of these growth factors. In this review, we address the role of TGFβ signaling in the developing limb, focusing on its essential function in the morphogenesis of the autopod. As we discuss in this work, modern mouse genetic experiments together with more classical embryological approaches in chick embryos, provided very valuable information concerning the role of TGFβ and Activin family members in the morphogenesis of the digits of tetrapods, including the formation of phalanxes, digital tendons, and interphalangeal joints. We emphasize the importance of the Activin and TGFβ proteins as digit inducing factors and their critical interaction with the BMP signaling to sculpt the hand and foot morphology.     

CD117阴性的胃肠道间质瘤的超微结构特点及基因突变检测

目的探讨CD117阴性的胃肠道间质瘤（GIST）的超微结构及c-kit和血小板源性生长因子受体A（PDGFRA）基因的突变情况。方法用免疫组织化学方法（EnVision法和SP法）从101例GIST中筛选到6例CD117阴性的GIST,观察了6例CD117阴性的胃肠道间质瘤的电镜变化,用PCR直接测序的方法检测6例CD117阴性的胃肠道间质瘤的c-kit基因外显子9、11、13、17和PDGFRA基因外显子12和18突变。结果电镜下观察到6例GIST的超微结构特点与卡哈尔细胞相似,通过PCR直接测序检测揭示c-kit基因9、11、13和17外显子均无突变,而3例GIST的PDGFRA有突变,其中2例D842V突变,1例R841S突变。结论PDGFRA基因的突变可能是CD117阴性的胃肠道间质瘤发生的重要分子基础。     

转化生长因子β1对乳鼠心肌细胞转化生长因子结合蛋白2表达的影响

 目的：探讨转化生长因子β1（TGF-β1）在诱导心肌细胞表达转化生长因子结合蛋白2（LTBP2）中的作用及信号传导通路。 方法：培养乳鼠心肌细胞;实时定量聚合酶链式反应（Real-time PCR）、蛋白质印迹和免疫细胞化学方法检测不同时间和不同浓度的TGF-β1对大鼠乳鼠心肌细胞LTBP2基因及蛋白表达的影响;用TGF-β1相关信号通路阻断剂探讨TGF-β1调节LTBP2表达改变的信号传导机制。 结果：LTBP2基因表达随着TGF-β1浓度增加（0、2、5、10 ng/mL）而明显升高,在5 ng/mL时刺激最强（P < 0.05）;5 ng/mL的TGF-β1刺激下心肌细胞内LTBP2基因和蛋白表达的升高呈时间依赖性,均在12 h最高,24 h开始呈下降趋势（P < 0.05或P<0.01）;免疫细胞化学结果显示TGF-β1明显升高LTBP2的表达。信号传导通路研究显示TGF-β1在心肌细胞内主要通过ERK信号通路和PI3K信号通路诱导LTBP2的表达。 结论：TGF-β1在乳鼠心肌细胞内通过ERK信号通路和PI3K信号通路上调LTBP2的表达。     

大鼠皮肤创伤修复过程中转化生长因子β1和β3的表达

背景：转化生长因子β在组织创伤修复中发挥核心和关键作用。 目的：观察转化生长因子β1和转化生长因子β3在大鼠皮肤瘢痕性创伤愈合过程中表达量及表达部位的变化。 方法：制备大鼠皮肤全层切伤模型,长度1.5-2.0 cm,深及筋膜层。于伤后0 h,12 h,1 d,2 d,3 d,4 d,5 d,6 d,7 d处死大鼠,取损伤部位皮肤,采用免疫组织化学染色检测各时间点转化生长因子β1和转化生长因子β3的表达,并进行定量分析。 结果与结论：免疫组织化学染色显示,在创伤愈合的早期阶段(伤后1-5 d),转化生长因子β1和转化生长因子β3免疫阳性颗粒主要出现在上皮细胞、上皮基底层细胞胞浆、巨噬细胞等免疫细胞胞浆及肉芽组织中;随着创伤修复时间的持续,免疫阳性颗粒主要出现在真皮层的成纤维细胞及细胞外基质中。其中转化生长因子β1的表达在创伤后1-5 d最强,而转化生长因子β3在创伤后六七天时开始明显表达。可见在大鼠皮肤瘢痕性创伤愈合过程中,转化生长因子β1的表达先于转化生长因子β3,提示转化生长因子β1与胶原形成及创伤修复关系密切,而转化生长因子β3在愈合后期表达量有升高趋势,其可能与创伤后期的组织改建密切相关。     

Embryonic expression of the transforming growth factor beta ligand and receptor genes in chicken

Results: Here we report the embryonic mRNA expression patterns in chicken embryos of the canonical TGFβ ligands (TGFB1, TGFB2, and TGFB3) and receptors (TGFBR1, TGFBR2, TGFBR3), plus the Activin A receptor, type 1 (ACVR1) and co receptor Endoglin (ENG) that also transduce TGFβ signaling. 相似文献   

Genetic alterations in colorectal cancers with demethylation of insulin-like growth factor II

Loss of genomic imprinting is an epigenetic alteration of some cancers involving the absence of parental origin–specific expression of imprinted genes. Loss of genomic imprinting of insulin-like growth factor II is often detected in colorectal cancer. However, the genetic alterations accompanied by colorectal cancer with insulin-like growth factor II loss of genomic imprinting have not been fully determined. Genomic DNA samples were collected from 52 colorectal cancer tissues and analyzed. The loss of insulin-like growth factor II genomic imprinting status was determined by assessing the demethylation of the insulin-like growth factor II differentially methylated region using bisulfite sequencing. The molecular signatures were also examined: genetic mutations of KRAS, BRAF, and PIK3CA; the expression of CTNNB1 and TP53; and microsatellite instability status. Several cases of colorectal cancer with normal insulin-like growth factor II imprinting were located in the distal colon; in contrast, colorectal cancer with loss of genomic imprinting tended to be found in the proximal colon (22.7 versus 56.6%). The PIK3CA gene mutation was highly detected in normal imprinting tumors compared to colorectal cancers with insulin-like growth factor II loss of genomic imprinting (27.3% versus 6.7%). In multivariate analysis of these clinicopathologic and molecular factors of tumors, statistically significant relationships were observed among the proximal location of the tumor (odds ratio, 12.9; 95% confidence interval, 1.52-110.13), PIK3CA genetic mutation (odds ratio, 0.082; 95% confidence interval, 0.01-0.73), and insulin-like growth factor II genomic imprinting status. Our findings indicate that colorectal cancers with demethylation of the insulin-like growth factor II gene are distinct from normal imprinting tumors, both in clinical and genetic features.     

Transforming growth factor Beta2 is required for valve remodeling during heart development

Although the function of transforming growth factor beta2 (TGFβ2) in epithelial mesenchymal transition (EMT) is well studied, its role in valve remodeling remains to be fully explored. Here, we used histological, morphometric, immunohistochemical and molecular approaches and showed that significant dysregulation of major extracellular matrix (ECM) components contributed to valve remodeling defects in Tgfb2^?/? embryos. The data indicated that cushion mesenchymal cell differentiation was impaired in Tgfb2^?/? embryos. Hyaluronan and cartilage link protein‐1 (CRTL1) were increased in hyperplastic valves of Tgfb2^?/? embryos, indicating increased expansion and diversification of cushion mesenchyme into the cartilage cell lineage during heart development. Finally, Western blot and immunohistochemistry analyses indicate that the activation of SMAD2/3 was decreased in Tgfb2^?/? embryos during valve remodeling. Collectively, the data indicate that TGFβ2 promotes valve remodeling and differentiation by inducing matrix organization and suppressing cushion mesenchyme differentiation into cartilage cell lineage during heart development. Developmental Dynamics 240:2127–2141, 2011. © 2011 Wiley‐Liss, Inc.     

Epidermal growth factor receptor mutations in lung cancers

In 2004, two groups reported somatic mutations in the gene for the epidermal growth factor receptor (EGFR) in patients with non-small cell lung cancer (NSCLC), which were highly correlated with the clinical response to the anticancer drug, gefitinib. Since then, a tremendous amount of knowledge has accumulated, and sheds light on significant oncological properties as well as the clinical relevance of this mutation, which could be applicable to other malignancies. The EGFR mutations are distributed throughout the kinase domain, but a deletion in exon 19 and the point mutation L858R in exon 21 account for approximately 90%, which confer a greater response to gefitinib treatment, compared with other types of EGFR mutations. These EGFR mutations in the tyrosine kinase domain are seldom acquired in cancers of the other organs and the mutations preferentially involve a subset of lung cancers, which are clinicopathologically characterized by female sex, non-smoking, adenocarcinoma histology and East Asian ethnicity. In Japan, the EGFR mutations are detected in approximately 30% of overall NSCLC and approximately 40% of surgically resected adenocarcinomas. The morphological features of adenocarcinomas harboring the mutations were reported to be frequent in those with bronchioloalveolar features, but it is suggested that the cellular lineage of the putative original cells of the cancers refines the subset more clearly. In the present study the current knowledge of EGFR mutations is reviewed, insights from which raise many further questions, and thus suggest new directions for future research.     

Transforming growth factor alpha and epidermal growth factor in human pancreatic cancer.

Overexpression of the epidermal growth factor receptor (EGFR) has been reported as an important molecular abnormality in human pancreatic cancer. There is in vitro evidence that simultaneous overproduction of one of its ligands, transforming growth factor alpha (TGF-alpha), might result in an autocrine loop with an increased proliferation signal. We analysed by immunocytochemical staining a retrospective series of human pancreatic cancers, chronic pancreatitis, and normal fetal and adult pancreatic tissues for the presence of TGF-alpha and epidermal growth factor (EGF). Ductal epithelial cells showed TGF-alpha immunoreactivity in both normal tissue and chronic pancreatitis, and 95 per cent of tumours showed strong immunoreactivity. In contrast, EGF immunoreactivity was not found in normal pancreas, but was expressed in 12 per cent of pancreatic carcinomas. Well-defined areas of EGF immunoreactivity in exocrine ducts showing reactive changes in pancreatitis might represent a benign response to tissue damage similar to that previously described in the gastric mucosa.