Nuclear factor I transcription factors regulate IGF binding protein 5 gene transcription in human osteoblasts.
Nuclear factor I transcription factors regulate IGF binding protein 5 gene transcription in human osteoblasts.
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DOI：
10.1016/j.bbagrm.2008.08.013
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发表时间：
2009-02
影响因子：
4.7
通讯作者：
Linkhart, Thomas A.
中科院分区：
文献类型：
--
作者：
Perez-Casellas, Laura A.;Wang, Xiaoying;Howard, Kristy D.;Rehage, Mark W.;Strong, Donna D.;Linkhart, Thomas A.
胰岛素样生长因子结合蛋白5（IGFBP 5）在包括成骨细胞在内的许多细胞类型中表达，并调节IGF活性。IGFBP 5可能影响成骨细胞和骨形成，部分通过独立于结合IGFs的机制。在转录起始的100个核苷酸内的高度保守的IGFBP 5近端启动子包含C/EBP、Myb和AP-2的功能性顺式调控元件。我们报告的证据表明，一个功能性核因子I（NFI）顺式元件，介导激活或抑制IGFBP 5转录的NFI基因家族。所有四种NFI基因在人成骨细胞培养物和骨肉瘤细胞系中表达。用人IGFBP 5启动子荧光素酶报告基因和鼠Nfi表达载体共转染显示，Nfib在刺激转录方面最活跃。Nfix的活性较低，Nfia和Nfic具有抑制作用。使用siRNA敲低NFIB和NFIC表达分别降低和增加IGFBP 5表达。IGFBP 5启动子缺失和突变报告构建体的分析鉴定了功能性NFI顺式元件。所有四种NFI蛋白在电泳迁移率变动实验中结合NFI位点，并且在染色质免疫沉淀测定中结合NFI-B。结果表明，NFI蛋白是人成骨细胞中IGFBP 5表达的重要调节因子，因此在调节骨中IGFBP 5功能中起重要作用。
Insulin-like growth factor binding protein 5 (IGFBP5) is expressed in many cell types including osteoblasts and modulates IGF activities. IGFBP5 may affect osteoblasts and bone formation, in part by mechanisms independent of binding IGFs. The highly conserved IGFBP5 proximal promoter within 100 nucleotides of the start of transcription contains functional cis regulatory elements for C/EBP, Myb and AP-2. We report evidence for a functional Nuclear Factor I (NFI) cis element that mediates activation or repression of IGFBP5 transcription by the NFI gene family. All four NFI genes were expressed in human osteoblast cultures and osteosarcoma cell lines. Co-transfection with human IGFBP5 promoter luciferase reporter and murine Nfi expression vectors showed that Nfib was the most active in stimulating transcription. Nfix was less active and Nfia and Nfic were inhibitory. Knockdown of NFIB and NFIC expression using siRNA decreased and increased IGFBP5 expression, respectively. Analysis of IGFBP5 promoter deletion and mutation reporter constructs identified a functional NFI cis element. All four NFI proteins bound the NFI site in electrophoretic mobility shift experiments and NFI-B bound in Chromatin Immunoprecipitation assays. Results suggest that NFI proteins are important regulators of IGFBP5 expression in human osteoblasts and thus in modulating IGFBP5 functions in bone.
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影响因子：
3.7
作者：
Cesi, V;Giuffrida, ML;Raschellà, G
通讯作者：
Raschellà, G
DOI：
10.1152/ajpendo.00648.2007
发表时间：
2008-01-01
影响因子：
5.1
作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
4.1
作者：
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通讯作者：
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DOI：
10.1152/ajpendo.1998.275.2.e222
发表时间：
1998-08-01
影响因子：
5.1
作者：
Gabbitas, B;Canalis, E
通讯作者：
Canalis, E