Mechanosensitive promoter region in the human HB-GAM gene

Mechanosensitive promoter region in the human HB-GAM gene
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DOI:
10.1016/j.bbrc.2009.07.002
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发表时间:
2009-09-18
影响因子:
3.1
通讯作者:
Ignatius, Anita
Ignatius, Anita
中科院分区:
生物学4区
文献类型:
--
作者:
Liedert, Astrid;Kassem, Moustapha;Ignatius, Anita

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机械负荷对于维持成人骨骼中的骨量是必不可少的。然而,物理刺激转化为生化反应的基本过程,这被称为机械转导知之甚少。机械转导通过机械敏感基因启动子区的特异性转录因子结合位点调节基因表达。在本研究中,我们证明了HB-GAM的表达,这是已知的成骨分化的刺激作用,是快速诱导hMSC-TERT 4细胞的机械负荷。用荧光素酶报告基因分析人HB-GAM基因上游调控区,发现HB-GAM表达的上调发生在转录水平,主要依赖于HB-GAM启动子区最上游含有三个潜在的AP-1结合基序。(C)2009 Elsevier Inc. All rights reserved.
Mechanical loading is essential for maintaining bone mass in the adult skeleton. However, the underlying process of the transfer of the physical stimulus into a biochemical response, which is termed mechanotransduction is poorly understood. Mechanotransduction results in the modulation of gene expression through specific transcription factor binding sites in the promoter region of mechanosensitive genes. In the present study, we demonstrate that the expression of HB-GAM, which is known to have stimulating effects on osteogenic differentiation, is rapidly induced by mechanical loading in hMSC-TERT4 cells. Analysis of the human HB-GAM gene upstream regulatory region with luciferase reporter gene assays revealed that the upregulation of HB-GAM expression occurred at the transcriptional level and was mainly dependent on the HB-GAM promoter region most upstream containing three potential AP-1 binding motifs. (C) 2009 Elsevier Inc. All rights reserved.