西班牙CORDOBA大学 通过抑制Wnt/β-Catenin信号路径，镁有抑制和逆转血管钙化的作用（和因而有抗癌作用，见相关研究 ）

Magnesium Inhibits Wnt/β-Catenin Activity and Reverses the Osteogenic Transformation of Vascular Smooth Muscle Cells

　

　

　

镁可降低体外血管平滑肌细胞（VSMC）钙化，但迄今尚未揭示其机制。这项研究仅使用了稍微增加的镁水平，目的在于确定：a）抑制镁向细胞内的转运是否影响VSMC钙化，b）Wnt /β-catenin信号传导（成骨分化的关键介质）是否被镁和c修饰。镁是否会影响已经建立的血管钙化。用高磷酸盐（3.3 mM）和适度升高的镁（1.4 mM）孵育的人VSMC可显着降低VSMC钙化和成骨转录因子Cbfa-1和osterix的表达，并上调天然钙化抑制剂基质Gla蛋白（MGP）的表达）和骨保护素（OPG）。在用细胞镁转运抑制剂（2-氨基乙氧基-二苯硼酸盐[2-APB]）培养的VSMC中，不再观察到镁对钙化和成骨标记物表达的保护作用。高磷酸盐诱导Wnt /β-catenin途径的激活，如β-catenin易位到核内，frizzled-3基因的表达增加以及Dkk-1基因的下调所证实的，Dkk-1基因是Wnt /β-的特异性拮抗剂连环蛋白信号通路。然而，镁的添加抑制了磷酸盐诱导的Wnt /β-连环蛋白信号传导途径的活化。此外，使用siRNA沉默TRPM7导致Wnt /β-catenin信号通路的激活。进行了其他实验，以测试镁在体外阻止已建立的VSMC钙化进程的能力。与对照组相比，延迟添加镁降低了钙含量，下调了Cbfa-1和osterix，下调了MGP和OPG。添加2-APB时未观察到此效果。总之，镁通过细胞膜的转运对于抑制体外VSMC钙化非常重要。镁对Wnt /β-catenin的抑制是一种潜在的细胞内机制，通过这种机制可以实现这种抗钙化作用。

　

　

 

此外,TRPM7沉默用siRNA导致/β-catenin Wnt信号通路的激活。另外还做了一些实验来测试镁在体外阻止已经建立的VSMC钙化的能力。

 

与对照组相比，延迟添加镁降低了钙的含量，降低了Cbfa-1和osterix，上调了MGP和OPG。

 

当加入2-APB时，没有观察到这种效应。

 

综上所述，镁通过细胞膜的转运对于体外抑制VSMC钙化具有重要意义。

 

使用镁抑制Wnt /β-catenin是一个潜在的细胞内机制，以实现抗钙化的效应。

　

 

Magnesium Inhibits Wnt/β-Catenin Activity and Reverses the Osteogenic Transformation of Vascular Smooth Muscle Cells

　

Addy Montes de Oca, Fatima Guerrero, Julio M. Martinez-Moreno, Juan A. Madueño, Carmen Herencia, Alan Peralta, Yolanda Almaden , Ignacio Lopez, Escolastico Aguilera-Tejero, Kristina Gundlach, Janine Büchel, Mirjam E. Peter, Jutta Passlick-Deetjen, Mariano Rodriguez, Juan R. Muñoz-Castañeda

Published: February 25, 2014https://doi.org/10.1371/journal.pone.0089525

 

Magnesium reduces vascular smooth muscle cell (VSMC) calcification in vitro but the mechanism has not been revealed so far. This work used only slightly increased magnesium levels and aimed at determining: a) whether inhibition of magnesium transport into the cell influences VSMC calcification, b) whether Wnt/β-catenin signaling, a key mediator of osteogenic differentiation, is modified by magnesium and c) whether magnesium can influence already established vascular calcification. Human VSMC incubated with high phosphate (3.3 mM) and moderately elevated magnesium (1.4 mM) significantly reduced VSMC calcification and expression of the osteogenic transcription factors Cbfa-1 and osterix, and up-regulated expression of the natural calcification inhibitors matrix Gla protein (MGP) and osteoprotegerin (OPG). The protective effects of magnesium on calcification and expression of osteogenic markers were no longer observed in VSMC cultured with an inhibitor of cellular magnesium transport (2-aminoethoxy-diphenylborate [2-APB]). High phosphate induced activation of Wnt/β-catenin pathway as demonstrated by the translocation of β-catenin into the nucleus, increased expression of the frizzled-3 gene, and downregulation of Dkk-1 gene, a specific antagonist of the Wnt/β-catenin signaling pathway. The addition of magnesium however inhibited phosphate-induced activation of Wnt/β-catenin signaling pathway. Furthermore, TRPM7 silencing using siRNA resulted in activation of Wnt/β-catenin signaling pathway. Additional experiments were performed to test the ability of magnesium to halt the progression of already established VSMC calcification in vitro. The delayed addition of magnesium decreased calcium content, down-regulated Cbfa-1 and osterix and up-regulated MGP and OPG, when compared with a control group. This effect was not observed when 2-APB was added. In conclusion, magnesium transport through the cell membrane is important to inhibit VSMC calcification in vitro. Inhibition of Wnt/β-catenin by magnesium is one potential intracellular mechanism by which this anti-calcifying effect is achieved.

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0089525

　

　

β-catenin/ Wnt信号通路在促进肿瘤发生肝细胞癌的作用

谢l1，姜华，吴福。

作者信息

1

宁波市北仑区中医院，宁波315800。

摘要

β-catenin Wnt信号通路与癌症关系密切,在许多人类癌症异常激活。肝细胞癌(HCC)是世界上第三大癌症相关死亡的常见原因，但HCC的分子机制尚不清楚。目前的研究表明, 在肝癌的发展和恶化中Wnt /β-catenin信号通路发挥着关键作用。

　

　

Related study:

[Role of Wnt/β-catenin signaling pathway in promoting tumorigenesis of hepatocellular carcinoma].

[Article in Chinese]

Xie L1, Jiang H, Wu F.

Author information

1

Beilun District TCM hospital, Ningbo 315800, China.

Abstract

Wnt/β-catenin signaling pathway has a close relationship with cancer and is abnormally activated in many human cancers. Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death worldwide, but the molecular mechanisms of HCC are still poorly understood. Current studies indicate that Wnt/β-catenin signaling pathway plays a key role in the development and progression of HCC. Validating the role and mechanism of Wnt/β-catenin signaling pathway in HCC will provide a theoretical basis for early diagnosis and treatment of HCC. In this review, we summarize the role of Wnt/β-catenin signaling pathway in HCC and the progress of current researches

https://www.ncbi.nlm.nih.gov/pubmed/24968856