Wnt signaling plays an important role in embryogenesis and tumorgenesis. Although the mechanism about how Wnts transduce their signaling from receptor frizzled (Fz) to cytosol has not been understood, dishevelled (Dvl...Wnt signaling plays an important role in embryogenesis and tumorgenesis. Although the mechanism about how Wnts transduce their signaling from receptor frizzled (Fz) to cytosol has not been understood, dishevelled (Dvl) protein was considered as the intersection of Wnt signal traffic. In this study, we characterized the function of three domains (DIX,PDZ and DEP) of Dvl-1 in canonical Wnt signal transduction and Dvl-1 membrane translocation. It was found both DIX and DEP domain were sufficient to block Wnt-3a-induced LEF-1 transcriptional activity and free cytosol β-catenin accumulation; whereas PDZ domain and a functional mutant form of DEP domain (DEP-KM) had no effect on canonical Wnt signaling. In addition, when cotransfected with Fz-7, DEP domain, but not DIX, PDZ or DEP-KM, translocated and co-localized with Fz-7 to the plasma membrane, which was similar to Dvl-1. Furthermore, it was DEP domain that could block Fz-7-induced membrane translocation of Dvl- 1 via a possible competitive mechanism. These results strongly suggest that DEP domain is responsible for the membrane translocation of Dvl-1 protein upon Wnt signal stimulation.展开更多
目的探讨细胞表面糖蛋白酶诱导体cluster of differentiation 147(CD147)和基质金属蛋白酶-7(matrix metalloproteinase-7,MMP-7)在胆管癌组织中的表达及与临床病理特征的关系。方法选取行手术切除胆管癌且病理证实的109例患者的胆管癌...目的探讨细胞表面糖蛋白酶诱导体cluster of differentiation 147(CD147)和基质金属蛋白酶-7(matrix metalloproteinase-7,MMP-7)在胆管癌组织中的表达及与临床病理特征的关系。方法选取行手术切除胆管癌且病理证实的109例患者的胆管癌组织为胆管癌组,同期行胆管癌根治术的100例患者的癌旁正常胆管组织标本为对照组。采用Image-pro Plus 6. 0图像分析和免疫组织化学实验检测CD147和MMP-7在组织中的表达。结果胆管癌组细胞表面CD147和MMP-7的PU值均高于对照组,差异均具有统计学意义[(33. 9±9. 4) PU vs (12. 3±4. 3)PU,(57. 5±15. 4) PU vs (12. 2±2. 5) PU,均P <0. 01]。CD147和MMP-7表达在胆管癌患者性别、年龄和有无神经侵犯方面比较,差异均无统计学意义(均P> 0. 05),而在浸润深度、病理分化程度及TNM分期方面比较,差异均具有统计学意义(均P <0. 05)。结论 CD147和MMP-7在胆管癌组织中高表达,且与胆管癌浸润深度、病理分化程度及TNM分期有关。展开更多
目的评价膜结合O-酰基转移酶7(MBOAT7)rs641738多态性与非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)易感性的关系。方法围绕MBOAT7多态性与NAFLD相关性所实施的病例-对照研究开展文献检索,所涉及数据库有中国生物医...目的评价膜结合O-酰基转移酶7(MBOAT7)rs641738多态性与非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)易感性的关系。方法围绕MBOAT7多态性与NAFLD相关性所实施的病例-对照研究开展文献检索,所涉及数据库有中国生物医学数据库、PubMed、万方、中国知网及Web of Science。对发表时间在2018年4月20日(含)之前的相关文献进行检索。指定两名评价者独立完成对纳入文献的数据抽提工作。采用Revman 5.3和STAT 12.0软件进行Meta分析。结果共纳入6篇文献,含NAFLD患者2 365例,病例对照9 058例。Meta分析结果显示,在加性、显性、隐性或等位基因模型下,两组比较差异均无统计学意义(CC vs TT:OR=0.93;CC vs TC+TT:OR=0.96;CC+CT vs TT:OR=0.92;C vs T:OR=0.96)。依据种族不同进行亚族分析后,发现在高加索人和亚洲人中,MBOAT7 rs641738多态性与NAFLD发病率均无关联(P>0.05)。结论 MBOAT7 rs641738突变与NAFLD易感性无关联。展开更多
文摘Wnt signaling plays an important role in embryogenesis and tumorgenesis. Although the mechanism about how Wnts transduce their signaling from receptor frizzled (Fz) to cytosol has not been understood, dishevelled (Dvl) protein was considered as the intersection of Wnt signal traffic. In this study, we characterized the function of three domains (DIX,PDZ and DEP) of Dvl-1 in canonical Wnt signal transduction and Dvl-1 membrane translocation. It was found both DIX and DEP domain were sufficient to block Wnt-3a-induced LEF-1 transcriptional activity and free cytosol β-catenin accumulation; whereas PDZ domain and a functional mutant form of DEP domain (DEP-KM) had no effect on canonical Wnt signaling. In addition, when cotransfected with Fz-7, DEP domain, but not DIX, PDZ or DEP-KM, translocated and co-localized with Fz-7 to the plasma membrane, which was similar to Dvl-1. Furthermore, it was DEP domain that could block Fz-7-induced membrane translocation of Dvl- 1 via a possible competitive mechanism. These results strongly suggest that DEP domain is responsible for the membrane translocation of Dvl-1 protein upon Wnt signal stimulation.
文摘目的探讨细胞表面糖蛋白酶诱导体cluster of differentiation 147(CD147)和基质金属蛋白酶-7(matrix metalloproteinase-7,MMP-7)在胆管癌组织中的表达及与临床病理特征的关系。方法选取行手术切除胆管癌且病理证实的109例患者的胆管癌组织为胆管癌组,同期行胆管癌根治术的100例患者的癌旁正常胆管组织标本为对照组。采用Image-pro Plus 6. 0图像分析和免疫组织化学实验检测CD147和MMP-7在组织中的表达。结果胆管癌组细胞表面CD147和MMP-7的PU值均高于对照组,差异均具有统计学意义[(33. 9±9. 4) PU vs (12. 3±4. 3)PU,(57. 5±15. 4) PU vs (12. 2±2. 5) PU,均P <0. 01]。CD147和MMP-7表达在胆管癌患者性别、年龄和有无神经侵犯方面比较,差异均无统计学意义(均P> 0. 05),而在浸润深度、病理分化程度及TNM分期方面比较,差异均具有统计学意义(均P <0. 05)。结论 CD147和MMP-7在胆管癌组织中高表达,且与胆管癌浸润深度、病理分化程度及TNM分期有关。
文摘目的评价膜结合O-酰基转移酶7(MBOAT7)rs641738多态性与非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)易感性的关系。方法围绕MBOAT7多态性与NAFLD相关性所实施的病例-对照研究开展文献检索,所涉及数据库有中国生物医学数据库、PubMed、万方、中国知网及Web of Science。对发表时间在2018年4月20日(含)之前的相关文献进行检索。指定两名评价者独立完成对纳入文献的数据抽提工作。采用Revman 5.3和STAT 12.0软件进行Meta分析。结果共纳入6篇文献,含NAFLD患者2 365例,病例对照9 058例。Meta分析结果显示,在加性、显性、隐性或等位基因模型下,两组比较差异均无统计学意义(CC vs TT:OR=0.93;CC vs TC+TT:OR=0.96;CC+CT vs TT:OR=0.92;C vs T:OR=0.96)。依据种族不同进行亚族分析后,发现在高加索人和亚洲人中,MBOAT7 rs641738多态性与NAFLD发病率均无关联(P>0.05)。结论 MBOAT7 rs641738突变与NAFLD易感性无关联。