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Neural stem cell transplantation is a good method to treat stroke, but the mechanism is still unclear. Therefore, this study aims to explore the regulatory mechanism of VEGF overexpression in transplanted NSCs to promote the recovery of neural function in ischemic rats by regulating Wnt signal transduction pathways. We amplified VEGF gene fragments by PCR and transfected them into NSCs with Ad5 adenovirus. Rat brain IRI model was established by MCAO method, and VEGF transfected NSCs (VEGF-NSCs) were transplanted 24 h after successful IRI model. One week after the transplant, cognitive function was assessed using a neurological deficit score; Brain injury was assessed by histopathology; Photochemical and ELISA methods were used to detect oxidative stress markers and inflammatory factors, respectively. Western blotting has been detected in molecules of the Wnt signaling pathway. The results showed that the transduced NSCs express VEGF at least for 14 days. VEGF-NSCs transplantation (VNT) improved spatial learning and memory in rats, and inhibited oxidative stress injury, inflammatory response, and histopathological injury. VNT also resulted in significant changes in the phosphorylation levels of ß-catenin and GSK-3ß proteins, ultimately triggering activation of the Wnt signal transduction pathway. These results suggest that the neuroprotective effects of VNT may be related to the regulation of the Wnt signal transduction pathway.
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Isquemia Encefálica , Vía de Señalización Wnt , Ratas , Animales , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo , Ratas Sprague-Dawley , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Isquemia Encefálica/metabolismo , Infarto CerebralRESUMEN
WNT/CTNNB1 signaling regulates tissue development and homeostasis in all multicellular animals, but the underlying molecular mechanism remains incompletely understood. Specifically, quantitative insight into endogenous protein behavior is missing. Here, we combine CRISPR/Cas9-mediated genome editing and quantitative live-cell microscopy to measure the dynamics, diffusion characteristics and absolute concentrations of fluorescently tagged, endogenous CTNNB1 in human cells under both physiological and oncogenic conditions. State-of-the-art imaging reveals that a substantial fraction of CTNNB1 resides in slow-diffusing cytoplasmic complexes, irrespective of the activation status of the pathway. This cytoplasmic CTNNB1 complex undergoes a major reduction in size when WNT/CTNNB1 is (hyper)activated. Based on our biophysical measurements, we build a computational model of WNT/CTNNB1 signaling. Our integrated experimental and computational approach reveals that WNT pathway activation regulates the dynamic distribution of free and complexed CTNNB1 across different subcellular compartments through three regulatory nodes: the destruction complex, nucleocytoplasmic shuttling, and nuclear retention.
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Simulación por Computador , Modelos Biológicos , Transducción de Señal/fisiología , Análisis de la Célula Individual/métodos , Proteínas Wnt/metabolismo , beta Catenina/metabolismo , Línea Celular , Regulación de la Expresión Génica , Humanos , Mutación , Proteínas Wnt/genética , Vía de Señalización Wnt/fisiología , beta Catenina/genéticaRESUMEN
CTNNB1 (catenin ß-1, also known as ß-catenin) plays a dual role in the cell. It is the key effector of WNT/CTNNB1 signalling, acting as a transcriptional co-activator of TCF/LEF target genes. It is also crucial for cell adhesion and a critical component of cadherin-based adherens junctions. Two functional pools of CTNNB1, a transcriptionally active and an adhesive pool, can therefore be distinguished. Whether cells merely balance the distribution of available CTNNB1 between these functional pools or whether interplay occurs between them has long been studied and debated. While interplay has been indicated upon artificial modulation of cadherin expression levels and during epithelial-mesenchymal transition, it is unclear to what extent CTNNB1 exchange occurs under physiological conditions and in response to WNT stimulation. Here, we review the available evidence for both of these models, discuss how CTNNB1 binding to its many interaction partners is controlled and propose avenues for future studies.
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Adhesión Celular , Vía de Señalización Wnt , beta Catenina/metabolismo , Animales , Biomarcadores , Cadherinas/genética , Cadherinas/metabolismo , Adhesión Celular/genética , Transición Epitelial-Mesenquimal/genética , Regulación de la Expresión Génica , Humanos , Transporte de Proteínas , beta Catenina/genéticaRESUMEN
Astrotactin 1 (ASTN1) is known to serve a physiological role in neuronal migration; however its role in liver cancer remains to be determined. In the present study, ASTN1 levels were lower in liver cancer tissues compared with those in matching normal tissue. ASTN1 levels were negatively associated with microscopic vascular invasion, advanced clinical stage and a less favorable prognosis in patients with hepatocellular carcinoma (HCC). Furthermore, ASTN1 overexpression in a liver cancer cell line reduced the migratory and invasive capacity of the cells. Based on bioinformatics analysis, ASTN1 levels were negatively associated with the Wnt signaling pathway. In addition, ASTN1 downregulated the protein expression levels of ßcatenin, Tcell factor (TCF)1, TCF4, Jun protooncogene (Cjun), Myc protooncogene (Cmyc), cyclooxygenase2 (COX2), metalloproteinase (MMP)2, MMP9 and vascular endothelial growth factor (VEGF) protein levels, indicative of suppression of Wnt signaling. Furthermore, XAV939induced Wnt signaling suppression reversed the ASTN1mediated inhibition of invasion and migration in cells. Overexpression of ASTN1 in xenografts reduced cancer development as well as Wnt signaling. TIMER analysis showed that ASTN1 expression was negatively correlated with B cell, macrophage and neutrophil infiltrating levels in HCC. Together, the results of the present study showed that ASTN1 reduced the migratory and invasive capacity of liver cancer cells, potentially served as a candidate biomarker for diagnosis and prediction of the prognosis of HCC, and was associated with immune infiltration. Understanding the underlying mechanisms of action of ASTN1 may facilitate the development of novel strategies for prevention and treatment of liver cancer.
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Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Proteínas del Tejido Nervioso/genética , Receptores de Superficie Celular/genética , beta Catenina/genética , Adulto , Anciano , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Genes myc/genética , Factor Nuclear 1-alfa del Hepatocito/genética , Compuestos Heterocíclicos con 3 Anillos/farmacología , Humanos , Proteínas Quinasas JNK Activadas por Mitógenos/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Masculino , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/genética , Persona de Mediana Edad , Invasividad Neoplásica/genética , Invasividad Neoplásica/patología , Factor de Transcripción 4/genética , Vía de Señalización Wnt/efectos de los fármacos , Adulto JovenRESUMEN
Secreted frizzled-related proteins (Sfrps) are a family of secreted proteins that bind extracellularly to Wnt ligands and frizzled receptors. This binding modulates the Wnt signaling cascade, and Sfrps interact with their corresponding receptors. Sfrps are thought to play an important role in the pathological mechanism of cardiac disease such as myocardial infarction, cardiac remodeling, and heart failure. However, the overall role of Sfrps in cardiac disease is unknown. Some members of the Sfrps family modulate cellular apoptosis, angiogenesis, differentiation, the inflammatory process, and cardiac remodeling. In this review, we summarize the evidence of Sfrps association with cardiac disease. We also discuss how multiple mechanisms may underlie Sfrps being involved in such diverse pathologies.
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A Wnt signaling network governs early anterior-posterior (AP) specification and patterning of the deuterostome sea urchin embryo. We have previously shown that non-canonical Fzl1/2/7 signaling antagonizes the progressive posterior-to-anterior downregulation of the anterior neuroectoderm (ANE) gene regulatory network (GRN) by canonical Wnt/ß-catenin and non-canonical Wnt1/Wnt8-Fzl5/8-JNK signaling. This study focuses on the non-canonical function of the Wnt16 ligand during early AP specification and patterning. Maternally supplied wnt16 is expressed ubiquitously during cleavage and zygotic wnt16 expression is concentrated in the endoderm/mesoderm beginning at mid-blastula stage. Wnt16 antagonizes the ANE restriction mechanism and this activity depends on a functional Fzl1/2/7 receptor. Our results also show that zygotic wnt16 expression depends on both Fzl5/8 and Wnt/ß-catenin signaling. Furthermore, Wnt16 is necessary for the activation and/or maintenance of key regulatory endoderm/mesoderm genes and is essential for gastrulation. Together, our data show that Wnt16 has two functions during early AP specification and patterning: (1) an initial role activating the Fzl1/2/7 pathway that antagonizes the ANE restriction mechanism; and (2) a subsequent function in activating key endoderm GRN factors and the morphogenetic movements of gastrulation.
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Tipificación del Cuerpo/genética , Morfogénesis/genética , Erizos de Mar , Proteínas Wnt/fisiología , Animales , Embrión no Mamífero , Receptores Frizzled/genética , Receptores Frizzled/fisiología , Gastrulación/genética , Regulación del Desarrollo de la Expresión Génica , Mesodermo/embriología , Mesodermo/metabolismo , Placa Neural/embriología , Placa Neural/metabolismo , Erizos de Mar/embriología , Erizos de Mar/genética , Proteínas Wnt/genética , Vía de Señalización Wnt/fisiologíaRESUMEN
The spatiotemporal expression of Frizzled receptors is critical for patterning along the early anterior-posterior axis during embryonic development in many animal species. However, the molecular mechanisms that regulate the expression of Frizzled receptors are incompletely understood in any species. In this study, I examine how the expression of two Frizzled receptors, Fzl1/2/7 and Fzl5/8, is controlled by the Wnt signaling network which directs specification and positioning of early regulatory states along the anterior-posterior (AP) axis of sea urchin embryos. I used a combination of morpholino- and dominant negative-mediated interference to knock down each Wnt signaling pathway involved in the AP Wnt signaling network. I found that the expression of zygotic fzl5/8 as well as that of the anterior neuroectoderm gene regulatory network (ANE GRN) is activated by an unknown broadly expressed regulatory state and that posterior Wnt/ß-catenin signaling is necessary to down regulate fzl5/8's expression in posterior blastomeres. I show that zygotic expression of fzl1/2/7 in the equatorial ectodermal belt is dependent on an uncharacterized regulatory mechanism that works in the same cells receiving the TGF-ß signals patterning this territory along the dorsal-ventral axis. In addition, my data indicate that Fzl1/2/7 signaling represses its own expression in a negative feedback mechanism. Finally, we discovered that a balance between the activities of posterior Wnt8 and anterior Dkk1 is necessary to establish the correct spatial expression of zygotic fzl12/7 expression in the equatorial ectodermal domain during blastula and gastrula stages. Together, these studies lead to a better understanding of the complex interactions among the three Wnt signaling pathway governing AP axis specification and patterning in sea urchin embryos.
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Tipificación del Cuerpo/genética , Receptores Frizzled/genética , Receptores Frizzled/fisiología , Animales , Blastómeros/metabolismo , Blástula/metabolismo , Gástrula/metabolismo , Regulación del Desarrollo de la Expresión Génica/genética , Placa Neural/embriología , Erizos de Mar/embriología , Erizos de Mar/genética , Análisis Espacio-Temporal , Factores de Transcripción/metabolismo , Proteínas Wnt/metabolismo , Vía de Señalización WntRESUMEN
BACKGROUND: Asiaticoside is a compound isolated from Herb Centella asiatica, which has been shown to promote osteogenic differentiation of human periodontal ligament (hPDL) cells. This study investigated the molecular mechanism underlying the asiaticoside-induced osteogenic differentiation of hPDL cells. METHODS: hPDL cells were incubated with various concentrations of asiaticoside to test cell viability by MTT assay. The mRNA expression levels were analyzed by using quantitative real-time polymerase chain reaction (PCR). Osteogenic differentiation was determined by alkaline phosphatase activity assay and alizarin red staining. The subcellular localization of ß-catenin was analyzed by both immunofluorescence and western blot. RESULTS: The results showed that asiaticoside had no effect on the cell viability at any of the tested concentrations. Real-time PCR revealed that osterix (OSX) and dentin matrix protein1 (DMP1) mRNA were significantly enhanced by asiaticoside treatment. Alkaline phosphatase activity and in vitro mineralization were also significantly induced. Interestingly, asiaticoside dose-dependently increased WNT3A mRNA expression, but not WNT5A and WNT10B. The activation of Wnt signaling was shown to result in nuclear accumulation of ß-catenin as evaluated by immunofluorescence staining and western blot analysis. Pre-treatment with recombinant human Dickkopf1 (rhDKK1) inhibited asiaticoside-induced ß-catenin nuclear translocation and osteoblast marker gene expression. Moreover, rhDKK1 attenuated asiaticoside-induced DMP1 protein expression. CONCLUSION: The data demonstrate that asiaticoside induces osteogenic differentiation of hPDL cells by activating the Wnt/ß-catenin signaling pathway. The findings suggest that asiaticoside could be used as a novel therapeutic drug for periodontal tissue regeneration.
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Osteogénesis , Vía de Señalización Wnt , Fosfatasa Alcalina , Diferenciación Celular , Células Cultivadas , Humanos , Ligamento Periodontal , TriterpenosRESUMEN
The anterior neuroectoderm (ANE) in many deuterostome embryos (echinoderms, hemichordates, urochordates, cephalochordates, and vertebrates) is progressively restricted along the anterior-posterior axis to a domain around the anterior pole. In the sea urchin embryo, three integrated Wnt signaling branches (Wnt/ß-catenin, Wnt/JNK, and Wnt/PKC) govern this progressive restriction process, which begins around the 32- to 60-cell stage and terminates by the early gastrula stage. We previously have established that several secreted Wnt modulators of the Dickkopf and secreted Frizzled-related protein families (Dkk1, Dkk3, and sFRP-1/5) are expressed within the ANE and play important roles in modulating the Wnt signaling network during this process. In this study, we use morpholino and dominant-negative interference approaches to characterize the function of a novel Frizzled-related protein, secreted Frizzled-related protein 1 (sFRP-1), during ANE restriction. sFRP-1 appears to be related to a secreted Wnt modulator, sFRP3/4, that is essential to block Wnt signaling and establish the ANE in vertebrates. Here, we show that the sea urchin sFRP3/4 orthologue is not expressed during ANE restriction in the sea urchin embryo. Instead, our results indicate that ubiquitously expressed maternal sFRP-1 and Fzl1/2/7 signaling act together as early as the 32- to 60-cell stage to antagonize the ANE restriction mechanism mediated by Wnt/ß-catenin and Wnt/JNK signaling. Then, starting from the blastula stage, Fzl5/8 signaling activates zygotic sFRP-1 within the ANE territory, where it works with the secreted Wnt antagonist Dkk1 (also activated by Fzl5/8 signaling) to antagonize Wnt1/Wnt8-Fzl5/8-JNK signaling in a negative feedback mechanism that defines the outer ANE territory boundary. Together, these data indicate that maternal and zygotic sFRP-1 protects the ANE territory by antagonizing the Wnt1/Wnt8-Fzl5/8-JNK signaling pathway throughout ANE restriction, providing precise spatiotemporal control of the mechanism responsible for the establishment of the ANE territory around the anterior pole of the sea urchin embryo.
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Wnt signaling is essential for embryonic development and adult homeostasis in multicellular organisms. A conserved feature among Wnt family proteins is the presence of two structural domains. Within the N-terminal (NT) domain there exists a motif that is superimposable upon saposin-like protein (SAPLIP) family members. SAPLIPs are found in plants, microbes and animals and possess lipid surface seeking activity. To investigate the function of the Wnt3a saposin-like subdomain (SLD), recombinant SLD was studied in isolation. Bacterial expression of this Wnt fragment was achieved only when the core SLD included 82 NT residues of Wnt3a (NT-SLD). Unlike SAPLIPs, NT-SLD required the presence of detergent to achieve solubility at neutral pH. Deletion of two hairpin loop extensions present in NT-SLD, but not other SAPLIPs, had no effect on the solubility properties of NT-SLD. Far UV circular dichroism spectroscopy of NT-SLD yielded 50-60% α-helix secondary structure. Limited proteolysis of isolated NT-SLD in buffer and detergent micelles showed no differences in cleavage kinetics. Unlike prototypical saposins, NT-SLD exhibited weak membrane-binding affinity and lacked cell lytic activity. In cell-based canonical Wnt signaling assays, NT-SLD was unable to induce stabilization of ß-catenin or modulate the extent of ß-catenin stabilization induced by full-length Wnt3a. Taken together, the results indicate neighboring structural elements within full-length Wnt3a affect SLD conformational stability. Moreover, SLD function(s) in Wnt proteins appear to have evolved away from those commonly attributed to SAPLIP family members.
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Proteína Wnt3A/química , Humanos , Lípidos de la Membrana/genética , Lípidos de la Membrana/metabolismo , Unión Proteica , Dominios Proteicos , Estructura Secundaria de Proteína , Proteína Wnt3A/genética , Proteína Wnt3A/metabolismoRESUMEN
BACKGROUND: Wnt signal transduction pathway (Wnt STP) is a crucial intracellular pathway mainly due to its participation in important biological processes, functions, and diseases, i.e., embryonic development, stem-cell management, and human cancers among others. This is why Wnt STP is one of the highest researched signal transduction pathways. Study and analysis of its origin, expansion and gradual development to the present state as found in humans is one aspect of Wnt research. The pattern of development and evolution of the Wnt STP among various species is not clear till date. A phylogenetic tree created from Wnt STPs of multiple species may address this issue. RESULTS: In this respect, we construct a phylogenetic tree from modules of Wnt STPs of diverse species. We term it as the 'Module Tree'. A module is nothing but a self-sufficient minimally-dependent subset of the original Wnt STP. Authenticity of the module tree is tested by comparing it with the two reference trees. CONCLUSIONS: The module tree performs better than an alternative phylogenetic tree constructed from pathway topology of Wnt STPs. Moreover, an evolutionary emergence pattern of the Wnt gene family is created and the module tree is tallied with it to showcase the significant resemblances.
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Evolución Molecular , Vía de Señalización Wnt , Animales , Humanos , Modelos Biológicos , Filogenia , ARN Ribosómico 18S/genéticaRESUMEN
Anterior signaling centers help specify and pattern the early anterior neuroectoderm (ANE) in many deuterostomes. In sea urchin the ANE is restricted to the anterior of the late blastula stage embryo, where it forms a simple neural territory comprising several types of neurons as well as the apical tuft. Here, we show that during early development, the sea urchin ANE territory separates into inner and outer regulatory domains that express the cardinal ANE transcriptional regulators FoxQ2 and Six3, respectively. FoxQ2 drives this patterning process, which is required to eliminate six3 expression from the inner domain and activate the expression of Dkk3 and sFRP1/5, two secreted Wnt modulators. Dkk3 and low expression levels of sFRP1/5 act additively to potentiate the Wnt/JNK signaling pathway governing the positioning of the ANE territory around the anterior pole, whereas high expression levels of sFRP1/5 antagonize Wnt/JNK signaling. sFRP1/5 and Dkk3 levels are rigidly maintained via autorepressive and cross-repressive interactions with Wnt signaling components and additional ANE transcription factors. Together, these data support a model in which FoxQ2 initiates an anterior patterning center that implements correct size and positions of ANE structures. Comparisons of functional and expression studies in sea urchin, hemichordate and chordate embryos reveal striking similarities among deuterostome ANE regulatory networks and the molecular mechanism that positions and defines ANE borders. These data strongly support the idea that the sea urchin embryo uses an ancient anterior patterning system that was present in the common ambulacrarian/chordate ancestor.
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Tipificación del Cuerpo/genética , Regulación del Desarrollo de la Expresión Génica , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Placa Neural/embriología , Strongylocentrotus purpuratus/embriología , Animales , Blástula/embriología , Tipificación del Cuerpo/fisiología , Proteínas del Ojo/biosíntesis , Proteínas de Homeodominio/biosíntesis , Péptidos y Proteínas de Señalización Intracelular , Proteínas del Tejido Nervioso/biosíntesis , Proteínas/genética , Proteínas Wnt/metabolismo , Vía de Señalización Wnt/genética , Proteína Homeobox SIX3RESUMEN
Mesenchymal stem cells (MSCs) are multipotent cells that have been widely used in cell based transplantation therapy. The use of MSCs requires in vitro expansion in order to fulfill their regenerative capacity. Therefore the proliferative ability of MSCs is one of the key factors which determine MSC therapeutic efficacy. In the present study, we showed for the first time that lithium, a well-known antidepressant, reversibly promoted the proliferation of human bone marrow derived MSCs in vitro. MSCs treated with 5 mm lithium proliferated more rapidly than untreated cells without undergoing apoptosis. Lithium increased the proportion of cells in S phase as well as cyclin D1 expression. Mechanistic studies revealed that these effects were dependent upon the activation of the glycogen synthase kinase 3ß (GSK-3ß) mediated canonical Wnt pathway. Lithium induced Ser9 phosphorylation, which results in the inhibition of GSK-3ß activity, ß-catenin accumulation and Wnt pathway activation. Utilizing a specific GSK-3ß inhibitor SB216763 or siRNA-mediated inhibition of GSK-3ß produced effects similar to those induced by lithium. In contrast, either quercetin, an inhibitor of the ß-catenin/TCF pathway, or siRNA-mediated knockdown of ß-catenin abolished the proliferative effect of lithium, suggesting that lithium stimulates MSC proliferation via the GSK-3ß-dependent ß-catenin/Wnt pathway. Collectively, these studies elucidate a novel role of lithium, which may not only provide a simple and effective way to strengthen MSC transplantation therapy efficacy but also shed light on lithium's clinical application for the treatment of certain disorders resulting from ß-catenin/Wnt pathway suppression.
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Células de la Médula Ósea/fisiología , Glucógeno Sintasa Quinasa 3/fisiología , Litio/farmacología , Células Madre Mesenquimatosas/efectos de los fármacos , Vía de Señalización Wnt/fisiología , beta Catenina/fisiología , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Glucógeno Sintasa Quinasa 3 beta , Humanos , Células Madre Mesenquimatosas/fisiologíaRESUMEN
The precise orchestration of two opposing protein complexes - one in the cytoplasm (ß-catenin destruction complex) and the other at the plasma membrane (LRP6 signaling complex) - is critical for controlling levels of the transcriptional co-factor ß-catenin, and subsequent activation of the Wnt/ß-catenin signal transduction pathway. The Wnt pathway component Axin acts as an essential scaffold for the assembly of both complexes. How the ß-catenin destruction and LRP6 signaling complexes are modulated following Wnt stimulation remains controversial. A recent study in Science by He and coworkers reveals an underlying logic for Wnt pathway control in which Axin phosphorylation toggles a switch between the active and inactive states. This mini-review focuses on this and two other recent studies that provide insight into the initial signaling events triggered by Wnt exposure. We emphasize regulation of the ß-catenin destruction and LRP6 signaling complexes and propose a framework for future work in this area.
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Proteína Axina/metabolismo , Vía de Señalización Wnt/fisiología , beta Catenina/metabolismo , Animales , Humanos , Fosforilación , Unión Proteica , Transducción de Señal , Vía de Señalización Wnt/genética , beta Catenina/genéticaRESUMEN
Objective To study the expressions of foliate binding protein 1(Folbp1),Wnt and ?-catenin genes on the heart of offspring during the development of embryo,whose mother was deficient of folic acid.Methods Control group involving 18 rats and study group involving 18 rats were choosen from the total 36 adult female SD rats randomly copulate with the male normal rats after feeding different fodder for 2 weeks.The heart of the 13.5,17.5 days embryos and the newborns were obtained.The expressions of Folbp1,Wnt and ?-catenin genes mRNA at the 3 periods were evaluated by RT-PCR.Results The expressions of Folbp1,Wnt and ?-catenin genes mRNA of the study group were significantly weaker than those of the control group in heart of the 13.5,17.5 days embryos and the newborns(all P
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Objective To explore the effects of various dosage and multiple course of Dexamethasone(DEX) on the expressions of WNTs,?-catenin and glycogen synthase kmase-3?(GSK-3?) genes in the lung of premature rats on the 19th day of embryo.Methods Twelve pregnant SD rats were divided into 3 groups randomly:small dose DEX group,large dose DEX group and control group with 4 rats in each group.The rats in control group were injected with saline 9 g/L;rats in small dose DEX group were injected with DEX 0.4 mg/(kg?d),and the rats in large dose DEX group were injected with DEX 0.8 mg/(kg?d) after DEX was diluted to 0.5 mL with saline.On the 19th day of gestation,fetuses were surgically taken out.The reverse transcription polymerase chain reaction PCR method was used to detect expressions of WNT7b,WNT5a,WNT2,GSK-3? and ?-catenin genes mRNA.Results The expressions of WNT7b(0.55?0.19,0.64?0.54)and ?-catenin(2.03?0.58,2.40?0.89)genes mRNA in small dose DEX group and large dose DEX group were significantly higher than those of control group(WNT7b:0.18?0.10,?-catenin:1.77?0.54)(Pa
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Wnt signal transduction pathway plays a very important role in embryonic development, and its abnormality may lead to developmental defects and cellular malignant transformation. It has been shown that disturbances of the Wnt signal transduction pathway were significantly related to human neoplastic transformation. The core mechanism of the pathway abnormality was the accumulation of free ?-catenin protein in the cytoplasm and nucleus resulting in the expressions of specific target genes by downstream pathway. This paper reviews the composition and structural character, transduction and regulation of the Wnt signal pathway and its relation with human tumorigenesis.