Wnt/β-catenin信号传导通路与大肠癌的发生发展

<正>大肠癌的发生发展是一个多因素、多阶段、多基因改变逐渐累积的复杂过程。Wnt/β-catenin信号传导通路中某些关键成员的基因异常改变(突变或缺失),导致通路的异常激活,与大肠癌的发生发展密切相关。现针对Wnt/β-catenin信号传导通路与大肠癌发生发展的关系进行综述。     

Wnt/β-catenin信号通路主要成员及在昆虫中的功能

综述了Wnt/β-catenin信号通路的主要组成成员,包括Wnt蛋白配体、Fzd(Frizzled)受体、LRP5/6(Low-density lipoprotein receptor-related protein 5/6)辅助受体、β-catenin、Axin、APC(Adenomatous polyposis coli)、GSK-3(Glycogen synthase kinase 3)、CK1(Casein kinase 1)、Dvl(Dishevelled)和TCF/LEF(T Cell Factor/Lymphoid Enhancer Factor)。同时概述了这些主要成员在昆虫上的研究概况以及在Wnt/β-catenin信号通路中的作用机制,并对该信号通路未来的研究进行了展望。     

Comment on "Activation of β-catenin in dendritic cells regulates immunity versus tolerance in the intestine"

Manicassamy et al. (Reports, 13 August 2010, p. 849) deleted β-catenin in intestinal immune cells using a CD11c-driven Cre recombinase, which decreased anti-inflammatory mediators and increased inflammatory bowel disease. However, the deletion of β-catenin in macrophages remains a caveat to their interpretation that Wnt signaling programs dendritic cells into a tolerogenic state. Development of strains expressing Cre in a more finely lineage-restricted pattern may help resolve this issue.     

Wnt/β-catenin信号途径与早期内胚层及相关器官的发育

介绍早期胚胎发育中Wnt/β-catenin信号途径对早期内胚层以及肝脏、胰腺、肠等内胚层器官发育的影响和相关的分子机制。     

抑制Wnt/β-catenin信号通路对始初小头虫再生的影响

wnt/β-catenin信号通路在涡虫等多种生物的再生中发挥重要作用,本研究以环节动物始初小头虫（Capitella teleta）为研究对象,初步探究wnt/β-catenin信号通路对小头虫再生的影响。将截断损伤后的样本持续浸泡于30 μM浓度外源性wnt/β-catenin信号通路小分子化合物抑制剂XAV-939中,发现小头虫的再生受到了抑制,与对照组相比再生速度明显减慢,且不能形成正常的再生芽基组织,通过神经和肌肉标记发现wnt信号通路被抑制后,小头虫再生过程中的神经、肌肉生长也受到了影响。后续通过EdU (5-Ethynyl-2’-deoxyuridine)标记发现抑制剂处理组样本的增殖细胞数量显著少于正常组样本,表明wnt/β-catenin信号通路被抑制后会影响小头虫再生过程中的增殖细胞产生,从而调控小头虫的再生调控过程。在几种典型物种中wnt通路调控再生的比较研究表明Wnt信号通路在刺胞动物和冠轮动物全身再生中的功能相对保守。     

壳寡糖对PM2.5染毒后小鼠肺和骨髓中Wnt/β-catenin信号通路表达的影响

目的 探讨壳寡糖对PM2.5染毒后小鼠肺和骨髓中Wnt/β-catenin信号通路相关蛋白表达的影响.方法 32只C57BL/6J小鼠随机分为空白对照组、模型组、壳寡糖组、阴性对照组.通过气管滴注法建立PM2.5染毒模型,壳寡糖(600 mg/kg)或双蒸水每天灌胃2周.HE染色观察肺、股骨及胫骨病理变化,Wester...     

福瑞鲤β-catenin2基因的克隆与表达分析

β-catenin是Wnt/β-catenin信号通路中的关键因子,参与调控性腺发育和分化。本研究首次克隆得到福瑞鲤(Cyprinus carpio)β-catenin2的c DNA全长序列,采用荧光定量PCR技术分析了β-catenin2基因的组织表达模式及注射外源性激素对福瑞鲤β-catenin2基因表达的影响。结果表明,β-catenin2 c DNA全长3 411 bp,编码780个氨基酸,预测分子量为85. 52 ku;实时荧光定量PCR表明,β-catenin2 mRNA在血液中表达量最高,其次是性腺和脾脏;且β-catenin2 mRNA表达量在福瑞鲤性腺发育早期,随着性腺发育的成熟而升高。睾丸甾酮(T)处理后发现:卵巢中β-catenin2 mRNA表达量在10μg/g 24 h处理组显著升高(P 0. 05),精巢中β-catenin2 mRNA表达量在10μg/g和50μg/g 24 h、48 h处理组显著降低(P 0. 05)。17β-雌二醇(E2)处理后发现:精巢和卵巢中β-catenin2 mRNA表达量无显著变化(P 0. 05);以上结果表明,β-catenin2在福瑞鲤性腺发育早期是必需的。     

Wnt10b、β-catenin、FGF18基因在‘甘肃高山细毛羊’胎儿皮肤毛囊中的表达规律研究

以81~147d胎龄的‘甘肃高山细毛羊’胚胎体侧部皮肤作为研究材料,通过冰冻切片、HE染色、荧光定量PCR、免疫组化技术研究Wnt10b、β-catenin、FGF18基因在次级毛囊形态发生过程中的表达规律.结果表明:从次级毛囊形态发生诱导期到器官形成阶段(胎龄87~108d)Wnt10b、FGF18基因表达量逐渐升高,在胎龄第108天Wnt10b、FGF18基因相对表达量分别达到(43.652±0.425)(13.67±0.207),在细胞分化期表达量逐渐下降;而β-catenin基因的表达量始终维持较低水平,相对表达量仅为(0.58±015);Wnt10b基因分别与β-catenin、FGF18基因表达水平呈显著正相关(r=0.85,P0.01;r=0.58,P0.05);β-catenin基因与FGF18基因表达水平呈正相关(r=0.43,P0.05).免疫组化结果显示在次级毛囊形态发生过程中Wnt10b、β-catenin基因主要在表皮、基板、毛芽、毛钉和成熟毛囊的内根鞘、毛干部表达;而FGF18不仅在表皮、基板、毛芽、毛钉和成熟毛囊的内根鞘、毛干部表达,而且在真皮中表达.本研究初步表明,Wnt10b、β-catenin、FGF18基因通过Wnt/β-catenin基因经典信号通路参与调控‘甘肃高山细毛羊’次级毛囊形态发生和再分化过程.     

Uterine Expression of WNT7A and β-catenin After Induction of Oestrus in Sheep

WNT7A and β-catenin localisations and roles in regulating periimplantation ovine conceptus development under natural estrous conditions have been elaborated.However,their locations and expression patterns have not been reported under induction of oestrus.The localisation,expression and function of WNT7A and β-catenin in the uterine tissues of the early pregnant and non-pregnant sheep on days 10,12,14,16 and 18 following artificial induction of oestrus were investigated by means of in situ hybridisation,real-time RT-PCR,immuno-histochemistry and western blotting methods.WNT7A and β-catenin mRNA and protein were both restricted to the apical surfaces of the uterine luminal epithelium (LE) and glandular epithelium (GE).In pregnant sheep,protein localisation of WNT7A and β-catenin was observed both in the endometrial LE and GE.Their staining presented on day 10,increased between day 12 and day 16,and decreased on day 18.WNT7A and β-catenin mRNA and protein expression increased initially and then decreased from day 10 to day 18,peaking on day 16,and β-catenin reaching a peak on day 18 in the uterine tissues of pregnant sheep (p0.05).By contrast,no significant changes in WNT7A and β-catenin mRNA and protein expression levels were observed from day 10 to day 18 of the oestrus cycle in the uterine tissues of non-pregnant sheep (p0.05).Additionally,WNT7A and β-catenin mRNA and protein expression levels in the uterine tissues of the early pregnant sheep were significantly higher than those of non-pregnant sheep (p0.05).Treatment of endometrial epithelial cells with WNT7A increased the mRNA expressions of β-catenin,c-myc and Cyclin D1.These results provided an underlying mechanism of periimplantation ovine conceptus development under induction of oestrus.     

Variations on conserved signaling pathways in biocontrol and development:G protein and MAPK genes of Trichoderma. atroviride and T. virens

Filamentous fungi employ conserved eukaryotic signaling pathway to detect and respond to environmental signals, including the presence of the host. Genetic experiment in which a particular signaling protein is lost, or its activity enhanced, have defined some of the function of heterotrimeric G proteins and MAP kinases in development and virulence. A hallmark of these studies is that orthologs in different species may have different functions. Antagonistic fungal-fungal interactions form …     

Kaempferol inhibits Pseudorabies virus replication in vitro through regulation of MAPKs and NF-κB signaling pathways

Pseudorabies virus(PRV), in the family Herpesviridae, is a pathogen of Aujeszky's disease, which causes great economic losses to the pig industry. Recent outbreaks of Pseudorabies imply that new control measures are urgently needed. The present study shows that kaempferol is a candidate drug for controlling PRV infection, as it possesses the ability to inhibit PRV replication in a dose-dependent manner in vitro. Kaempferol at a concentration of 52.40 μmol L–1 could decrease PRV-induced cell death by 90%. With an 50% inhibitory concentration(IC50) value of 25.57 μmol L–1, kaempferol was more effective than acyclovir(positive control) which has an IC50 value of 54.97 μmol L–1. A mode of action study indicated that kaempferol inhibited viral penetration and replication stages, decreasing viral loads by 4-and 30-fold, respectively. Addition of kaempferol within 16 h post infection(hpi) could significantly inhibit virus replication, and viral genome copies were decreased by almost 15-fold when kaempferol was added at 2 hpi. Kaempferol regulated the NF-κB and MAPKs signaling pathways involved in PRV infection and changed the levels of the target genes of the MAPKs(ATF-2 and c-Jun) and NF-κB(IL-1α, IL-1β and IL-2) signaling pathways. The findings of the current study suggest that kaempferol could be an alternative measure to control PRV infection.     

Biodiversity and distribution of Hypocrea/Trichoderma species in New Zealand

With increased imports of foreign microbes either as commercial biocontrol produ cts or for the purposes of research, there is potentially an increased threat to indigenous beneficial microflora. In the present study, indigenous species of t he fungal genus Hypocrea/Trichoderma are being used as a model system to d etermine the impact of foreign microbes on the native microflora of New Zealand. In order to protect such microflora, one has to first be aware of what is curre ntly present an…     

Depletion of conventional mature B cells and compromised specific antibody response in bovine immunoglobulin μ heavy-chain transgenic mice

In this study, we introduced the bovine immunoglobulin μ heavy-chain gene (the orphaned gene on BTA11) into mouse germline cells. Bovine IgM was highly expressed in selected transgenic lines, and it largely inhibited rearrangements of the endogenous immunoglobulin heavy chain (IgH) genes in these lines. The forced expression of bovine IgM resulted in reduced numbers of pro- and pre-B cells but increased the number of immature B cells in the transgenic mice. Bovine IgM-expressing B cells can migrate from the bone marrow to the spleen, but most of the cells are arrested at the T1 transitional B cell stage, leading to a significantly lower number of T2 transitional and mature B cells in the spleen. Although the serum concentrations of endogenous IgM and IgG in the transgenic mice were significantly decreased, the IgA levels were slightly increased compared to the WT mice. The bovine IgM level in the serum was only one-tenth to one-fifth of that of endogenous mouse IgM, suggesting that most of the serum immunoglobulin were contributed by endogenous IgH gene-expressing B cells. These transgenic mice also exhibited a lower frequency of unique complementarity determining region 3 (CDR3) sequences in their VH repertoire and Vκ repertoire but exhibited an increased frequency of unique CDR3 in their Vλ repertoire. Compared to the WT mice, the transgenic mice had a significantly higher percentage of mouse IgM-expressing B cells that expressed λ chains. Finally, we showed that the transgenic mice were deficient in a specific antibody response to antigen stimulation.     

The Variation ofβ-glucan and Protein Content in Barley as Affected by Agronomic Practices

The influences of N applicationrate, timing, sowing date and seeding rate on β-glucan and protein content in barley grains were studied through the field experiments in Hangzhou, China during 1997 -2001. Protein content increased with N application rate and with N proportion applied at late stage. β-glucan content also responded significantly to N application rate and timing, but with different pattern with protein content. Of three N rate treatments, the medium N rate (135 kg ha-1) had the highest β-glucan content, being significantly higher than low N rate (90 kg ha-1) and no difference with high N rate (180 kg ha-1). Among three N timing treatments, two times of N top-dressing at both tillering and booting stage had significantly higher β- glucan content than once N top-dressing at tillering or booting stage. Sowing date has the dramatic effect on both β-glucan and protein content. Protein content decreased with the delayed sowing, and kernel weight showed opposite tendency. Either earlier or later sowing caused increased β- glucan content relative to sowing in early November, which is the normal date for barley sowing locally. Seeding rate had no significant influence on both β- glucan and protein content.     

17β-Estradiol Regulates SKP2 Expression in Cultured Immature Boar Sertoli Cells Mainly via Estrogen Receptor β, cAMP-PKA and ERK1/2

Estrogen plays an important role in regulating testicular Sertoli cell number. Furthermore, S-phase kinase-associated protein 2 （SKP2） plays a central role in mammalian cell cycle progression. The objective of this study was to determine whether 17β-estradiol can regulate the expression of SKP2, and the Sertoli cell cycle, via estrogen receptor β （ERβ）, the cyclic adenosine monophosphate （cAMP）-protein kinase A （PKA） and extracellular signal-regulated kinase （ERK1/2） pathway. When cultured immature boar Sertoli cells were treated with 17β-estradiol, a time-dependent increase in SKP2 mRNA and protein level was observed by real-time PCR and Western blot, and 17β-estradiol activity peaked at 30 min. Treatment with ICI182780 and ERβ antagonist reduced 17β-estradiol-induced expression of SKP2 and proliferating cell nuclear antigen （PCNA）, while increasing the protein concentration of p27kip1. However, the effect of ERa antagonist on these parameters was lower than that of ICI 182780 and ERβ. Forskolin had a similar effect as 17β-estradiol on the expression of SKP2, PCNA and p27kip1, Rp-cAMP, H-89 and U0126 treatment reduced 17β-estradiol-induced changes, while H-89 also inhibited ERK1/2 activation. Therefore, 17β-estradiol mainly regulates SKP2 mRNA and protein expression via ERβ-cAMP-PKA and ERK1/2 activation. SKP2 and PCNA expression were positively correlated, while increased SKP2 expression likely resulted in p27kip1 degradation.