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维生素D是否通过内源性反义mRNA对Msx1同源蛋白表达发挥作用?

Does Vitamin D play a role on Msx1 homeoprotein expression involving an endogenous antisense mRNA?

作者信息

Lézot F, Coudert A, Petit S, Vi-Fane B, Hotton D, Davideau J L, Kato S, Descroix V, Pibouin L, Berdal A

机构信息

Laboratoire de Biologie Orofaciale et Pathologie, INSERM E 110, Institut Biomédical des Cordeliers, Université Paris 7, IFR58, 15-21 rue de l'Ecole de Médecine, 75006 Paris, France.

出版信息

J Steroid Biochem Mol Biol. 2004 May;89-90(1-5):413-7. doi: 10.1016/j.jsbmb.2004.03.116.

Abstract

Msx1 homeobox gene, a member of Msx family, has been implicated in numerous organs. Its participation was established in different events, such as morphogenetic field determinism and epithelio-mesenchymal interactions. Most of Msx1 target organs are also known for their sensitivity to Vitamin D: such as bone, tooth germ, and hair follicle. Whereas, the expression of Msx2, another member of Msx family, has been shown to be controlled by Vitamin D, no information is available for Msx1. This study aims to analyze the potential relationships between Vitamin D and Msx1 through: (1) comparative analysis of Vitamin D receptor (VDR) and Msx1 protein expression, (2) investigation of Msx1 expression in VDR null mutant mice, and (3) study of Msx1 overexpression impact on osteocalcin VDR expression in immortalized MO6-G3 odontoblasts. Results show the existence of cross-talks between Vitamin D and Msx1 regulation pathways. In odontoblastic cells, Msx1 overexpression decrease VDR expression, whereas in rickets Msx1 sense transcript expression is decreased. These cross-talks may open a new window in the analysis of rickets mineralized tissues physiopathology. In Vitamin D null mutants, the study of the natural Msx1 antisense transcript which has been recently described should be informative.

摘要

Msx1同源框基因是Msx家族的成员之一,与众多器官有关。它参与了不同的事件,如形态发生场的确定和上皮-间充质相互作用。Msx1的大多数靶器官也因其对维生素D敏感而闻名:如骨骼、牙胚和毛囊。然而,虽然已证明Msx家族的另一个成员Msx2的表达受维生素D控制,但关于Msx1的信息却尚无报道。本研究旨在通过以下方式分析维生素D与Msx1之间的潜在关系:(1)比较分析维生素D受体(VDR)和Msx1蛋白表达;(2)研究VDR基因敲除突变小鼠中Msx1的表达;(3)研究Msx1过表达对永生化MO6-G3成牙本质细胞中骨钙素VDR表达的影响。结果表明维生素D和Msx1调控途径之间存在相互作用。在成牙本质细胞中,Msx1过表达会降低VDR表达,而在佝偻病中Msx1有义转录本表达会降低。这些相互作用可能为分析佝偻病矿化组织的病理生理学打开一扇新窗口。在维生素D基因敲除突变体中,对最近描述的天然Msx1反义转录本的研究可能会提供有价值的信息。

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