The Wnt signaling pathway plays crucial roles during embryonic development, whose aberration is implicated in a variety of human cancers. Axin, a key component of canonical Wnt pathway, plays dual roles in modulat- in...The Wnt signaling pathway plays crucial roles during embryonic development, whose aberration is implicated in a variety of human cancers. Axin, a key component of canonical Wnt pathway, plays dual roles in modulat- ing Wnt signaling： on one hand, Axin scaffolds the ＂l^-catenin destruction complex＂ to promote 13-catenin degradation and therefore inhibits the Wnt signal transduction; on the other hand, Axin interacts with LRP5/6 and facilitates the recruitment of GSK3 to the plasma membrane to promote LRP516 phosphorylation and Wnt signaling. The differential assemblies of Axin with these two distinct complexes have to be tightly controlled for appropriate transduction of the ＂on＂ or ＂off＂ Wnt signal. So far, there are multiple mechanisms revealed in the regulation of Axin activity, such as post- transcriptional modulation, homo/hetero-polymerization and auto-inhibition. These mechanisms may work cooperatively to modulate the function of Axin, thereby playing an important role in controlling the canonical Wnt signaling. In this review, we will focus on the recent progresses regarding the regulation of Axin function in canonical Wnt signaling.展开更多
To examine the possible correlation of aberrant Wnt signaling and pathological changes in Alzheimer’s disease, we established a rat model of Alzheimer’s disease and measured axin and β-catenin expression in the hip...To examine the possible correlation of aberrant Wnt signaling and pathological changes in Alzheimer’s disease, we established a rat model of Alzheimer’s disease and measured axin and β-catenin expression in the hippocampus. Rats were pretreated with moxibustion or electroacu-puncture, or both, at Baihui（GV20） and Shenshu（BL23）. Axin expression was lower, β-catenin expression was greater, and neuronal cytoplasmic edema was visibly prevented in the rats that had received the pretreatments. Our results suggest that the mechanism underlying the neuro-protective effect of acupuncture and moxibustion in Alzheimer’s disease is associated with axin and β-catenin expression in the Wnt signal transduction pathway.展开更多
目的探讨轴抑制因子(AXIN)通过β-catenin调控MMP7、MMP9对淋巴瘤细胞侵袭迁移能力的影响。方法用RT-PCR和Western blot法观察多株淋巴瘤细胞株里AXIN、β-catenin、MMP7、MMP9的表达情况;选取AXIN相对低表达的淋巴瘤细胞分组瞬时转染p ...目的探讨轴抑制因子(AXIN)通过β-catenin调控MMP7、MMP9对淋巴瘤细胞侵袭迁移能力的影响。方法用RT-PCR和Western blot法观察多株淋巴瘤细胞株里AXIN、β-catenin、MMP7、MMP9的表达情况;选取AXIN相对低表达的淋巴瘤细胞分组瞬时转染p CMV5-HA-Axin和pc DNA5-His-β-catenin质粒,采用RT-PCR和Western blot法观察其细胞中β-catenin、MMP7、MMP9 m RNA及蛋白表达变化;构建稳定高表达AXIN的淋巴瘤细胞后,分组瞬时转染AXIN-sh RNA和β-catenin-sh RNA后观察β-catenin、MMP7、MMP9 m RNA及蛋白变化;采用Transwell侵袭实验观察空白处理对照组、稳定高表达AXIN组、干扰AXIN的稳定高表达AXIN组细胞侵袭和迁移能力变化。结果多株淋巴瘤细胞株中AXIN与β-catenin、MMP7、MMP9表达呈负相关;选用AXIN相对低表达的人恶性B淋巴瘤细胞株Raji,过表达AXIN后发现AXIN升高后,β-catenin、MMP7、MMP9的蛋白表达降低,MMP7、MMP9、β-catenin m RNA未变化;当过表达β-catenin后发现MMP7、MMP9 m RNA和蛋白表达升高;另外,稳定高表达AXIN的细胞中干扰AXIN,β-catenin、MMP7、MMP9蛋白表达升高,MMP7、MMP9、β-catenin m RNA未变化;稳定高表达AXIN的细胞中干扰β-catenin,MMP7、MMP9表达降低;证实AXIN通过β-catenin调控MMP7、MMP9影响淋巴瘤细胞的侵袭和迁移。结论在淋巴瘤细胞中升高AXIN可引起β-catenin表达下降,进而MMP7、MMP9表达下降,抑制淋巴瘤细胞的侵袭和迁移。展开更多
OBJECTIVE:To investigate the protective effect of the Chinese herbal formula of Jiedu Huayu decoction(解毒化瘀汤,JHD)on oral mucosa of rats with oral submucosal fibrosis(OSF)and its potential mechanism of action.METHO...OBJECTIVE:To investigate the protective effect of the Chinese herbal formula of Jiedu Huayu decoction(解毒化瘀汤,JHD)on oral mucosa of rats with oral submucosal fibrosis(OSF)and its potential mechanism of action.METHODS:Sprague-Dawley male OSF model rats were constructed by injection of betaine and topical rubbing and were randomly grouped and administered by gavage for 4 weeks.Mouth opening and buccal mucosa scores interleukin levels and the expression of Axin andβ-catenin proteins or genes were measured before and after drug administration.RESULTS:After treatment with JHD the buccal mucosal lesions of rats were significantly reduced Axin protein and mRNA expression were significantly increasedβ-catenin protein and m RNA expression were significantly decreased interleukin-1βand interleukin-6 levels were decreased and interleukin-10 levels were increased.CONCLUSION:The mechanism of action of JHD can effectively alleviate the pathological damage of buccal mucosa in OSF rats which may be related to the promotion of Axin expression and inhibition ofβ-catenin expression.展开更多
文摘The Wnt signaling pathway plays crucial roles during embryonic development, whose aberration is implicated in a variety of human cancers. Axin, a key component of canonical Wnt pathway, plays dual roles in modulat- ing Wnt signaling： on one hand, Axin scaffolds the ＂l^-catenin destruction complex＂ to promote 13-catenin degradation and therefore inhibits the Wnt signal transduction; on the other hand, Axin interacts with LRP5/6 and facilitates the recruitment of GSK3 to the plasma membrane to promote LRP516 phosphorylation and Wnt signaling. The differential assemblies of Axin with these two distinct complexes have to be tightly controlled for appropriate transduction of the ＂on＂ or ＂off＂ Wnt signal. So far, there are multiple mechanisms revealed in the regulation of Axin activity, such as post- transcriptional modulation, homo/hetero-polymerization and auto-inhibition. These mechanisms may work cooperatively to modulate the function of Axin, thereby playing an important role in controlling the canonical Wnt signaling. In this review, we will focus on the recent progresses regarding the regulation of Axin function in canonical Wnt signaling.
基金supported by the National Natural Science Foundation of China,No.30772837the Wuhan Municipal"Morning Sun"Science and Technology Plan,No.200850731347
文摘To examine the possible correlation of aberrant Wnt signaling and pathological changes in Alzheimer’s disease, we established a rat model of Alzheimer’s disease and measured axin and β-catenin expression in the hippocampus. Rats were pretreated with moxibustion or electroacu-puncture, or both, at Baihui（GV20） and Shenshu（BL23）. Axin expression was lower, β-catenin expression was greater, and neuronal cytoplasmic edema was visibly prevented in the rats that had received the pretreatments. Our results suggest that the mechanism underlying the neuro-protective effect of acupuncture and moxibustion in Alzheimer’s disease is associated with axin and β-catenin expression in the Wnt signal transduction pathway.
文摘目的探讨轴抑制因子(AXIN)通过β-catenin调控MMP7、MMP9对淋巴瘤细胞侵袭迁移能力的影响。方法用RT-PCR和Western blot法观察多株淋巴瘤细胞株里AXIN、β-catenin、MMP7、MMP9的表达情况;选取AXIN相对低表达的淋巴瘤细胞分组瞬时转染p CMV5-HA-Axin和pc DNA5-His-β-catenin质粒,采用RT-PCR和Western blot法观察其细胞中β-catenin、MMP7、MMP9 m RNA及蛋白表达变化;构建稳定高表达AXIN的淋巴瘤细胞后,分组瞬时转染AXIN-sh RNA和β-catenin-sh RNA后观察β-catenin、MMP7、MMP9 m RNA及蛋白变化;采用Transwell侵袭实验观察空白处理对照组、稳定高表达AXIN组、干扰AXIN的稳定高表达AXIN组细胞侵袭和迁移能力变化。结果多株淋巴瘤细胞株中AXIN与β-catenin、MMP7、MMP9表达呈负相关;选用AXIN相对低表达的人恶性B淋巴瘤细胞株Raji,过表达AXIN后发现AXIN升高后,β-catenin、MMP7、MMP9的蛋白表达降低,MMP7、MMP9、β-catenin m RNA未变化;当过表达β-catenin后发现MMP7、MMP9 m RNA和蛋白表达升高;另外,稳定高表达AXIN的细胞中干扰AXIN,β-catenin、MMP7、MMP9蛋白表达升高,MMP7、MMP9、β-catenin m RNA未变化;稳定高表达AXIN的细胞中干扰β-catenin,MMP7、MMP9表达降低;证实AXIN通过β-catenin调控MMP7、MMP9影响淋巴瘤细胞的侵袭和迁移。结论在淋巴瘤细胞中升高AXIN可引起β-catenin表达下降,进而MMP7、MMP9表达下降,抑制淋巴瘤细胞的侵袭和迁移。
基金Funding from Scientific Research Project of Hunan Provincial Education Department:to Investigate the Mechanism of Blood-activating Circulation Through the Regulation of Blood Stasis and Detoxification based on Wntβ-catenin Signaling Pathway(No.21B0398)Study on the Epithelial Mesenchymal Transformation of Human Umbilical Vein Endothelial Cells Induced by Fuxin Formula(No.22C0190)Changsha City 2020 Annual Guiding Science and Technology Plan Projects:Effect of Blood Circulation and Detoxification Method on Epithelial Barrier Composition and Function of Oral Mucosa(No.kzd2001010)。
文摘OBJECTIVE:To investigate the protective effect of the Chinese herbal formula of Jiedu Huayu decoction(解毒化瘀汤,JHD)on oral mucosa of rats with oral submucosal fibrosis(OSF)and its potential mechanism of action.METHODS:Sprague-Dawley male OSF model rats were constructed by injection of betaine and topical rubbing and were randomly grouped and administered by gavage for 4 weeks.Mouth opening and buccal mucosa scores interleukin levels and the expression of Axin andβ-catenin proteins or genes were measured before and after drug administration.RESULTS:After treatment with JHD the buccal mucosal lesions of rats were significantly reduced Axin protein and mRNA expression were significantly increasedβ-catenin protein and m RNA expression were significantly decreased interleukin-1βand interleukin-6 levels were decreased and interleukin-10 levels were increased.CONCLUSION:The mechanism of action of JHD can effectively alleviate the pathological damage of buccal mucosa in OSF rats which may be related to the promotion of Axin expression and inhibition ofβ-catenin expression.
