1,25-dihydroxyvitamin D(3) regulation of fibroblast growth factor-23 expression in bone cells: evidence for primary and secondary mechanisms modulated by leptin and interleukin-6.
1,25-dihydroxyvitamin D(3) regulation of fibroblast growth factor-23 expression in bone cells: evidence for primary and secondary mechanisms modulated by leptin and interleukin-6.
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DOI：
10.1007/s00223-012-9683-5
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发表时间：
2013-04
影响因子：
4.2
通讯作者：
Whitfield, G. Kerr
中科院分区：
文献类型：
--
作者：
Saini, Rimpi K.;Kaneko, Ichiro;Jurutka, Peter W.;Forster, Ryan;Hsieh, Antony;Hsieh, Jui-Cheng;Haussler, Mark R.;Whitfield, G. Kerr
关键词：
成纤维细胞生长因子-23（FGF 23）是一种循环激素，其通过抑制肾磷酸盐重吸收来纠正高磷酸盐血症，并通过反馈抑制1，25-二羟基维生素D3（1，25（OH）2D 3）生物合成来预防维生素D过多症。成骨细胞/骨细胞中的FGF 23基因表达由与1，25（OH）2D 3结合的核维生素D受体（VDR）诱导，但这种诱导的放线菌酮敏感性表明其可能主要通过需要协作转录因子的次级机制发生。因此，我们试图鉴定可能影响FGF 23表达的1，25（OH）2D 3调节的转录因子。尽管单独的瘦素和白细胞介素-6（IL-6）都不影响FGF 23表达，但发现瘦素处理增强UMR-106细胞中FGF 23的1，25（OH）2D 3上调，而IL-6处理减弱这种上调。基因组分析揭示了人和其他哺乳动物FGF 23基因中STAT（瘦素和IL-6作用的信号转导介质）沿着转录因子ETS 1的保守结合位点。此外，在UMR-106细胞中，1，25（OH）2D 3以剂量依赖性方式诱导STAT 3、STAT 1、ETS 1和VDR mRNA。生物信息学分析在含有人FGF 23的基因组间隔中鉴定了9个潜在的VDRE。当被1，25（OH）2D 3配体的VDR复合物结合时，6个推定的VDRE能够介导异源报告基因的直接转录激活。提出了一种模型，其中1，25（OH）2D 3通过多个VDRE直接上调FGF 23的产生，并通过诱导STAT 3、ETS 1和VDR转录因子间接上调FGF 23的产生，然后通过细胞表面和细胞内信号传导激活STAT 3、ETS 1和VDR转录因子，以通过DNA成环和常染色质结构的产生协同诱导FGF 23。
Fibroblast growth factor-23 (FGF23) is a circulating hormone that acts to correct hyperphosphatemic states by inhibiting renal phosphate reabsorption and to prevent hypervitaminosis D by feedback repressing 1, 25-dihydroxyvitamin D3 (1,25(OH)2D3) biosynthesis. FGF23 gene expression in the osteoblast/osteocyte is induced by the nuclear vitamin D receptor (VDR) bound to 1,25(OH)2D3, but cycloheximide sensitivity of this induction suggests that it may occur largely via secondary mechanisms requiring cooperating transcription factors. We therefore sought to identify 1,25(OH)2D3-regulated transcription factors that might impact FGF23 expression. Although neither leptin nor interleukin-6 (IL-6) alone affects FGF23 expression, leptin treatment was found to potentiate 1,25(OH)2D3 upregulation of FGF23 in UMR-106 cells, whereas IL-6 treatment blunted this upregulation. Genomic analyses revealed conserved binding sites for STATs (signal transduction mediators of leptin and IL-6 action) along with transcription factor ETS1 in human and other mammalian FGF23 genes. Further, STAT3, STAT1, ETS1, and VDR mRNAs were induced in a dose-dependent manner by 1,25(OH)2D3 in UMR-106 cells. Bioinformatic analysis identified nine potential VDREs in a genomic interval containing human FGF23. Six of the putative VDREs were capable of mediating direct transcriptional activation of a heterologous reporter gene when bound by a 1,25(OH)2D3-liganded VDR complex. A model is proposed wherein 1,25(OH)2D3 upregulates FGF23 production directly via multiple VDREs and indirectly via induction of STAT3, ETS1, and VDR transcription factors that are then activated via cell surface and intracellular signaling to cooperate in the induction of FGF23 through DNA looping and generation of euchromatin architecture.
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影响因子：
3
作者：
Liu, Wei-hua;Zhou, Qiao-ling;He, Nan
通讯作者：
He, Nan
DOI：
10.1152/ajpgi.00243.2005
发表时间：
2005-12-01
影响因子：
4.5
作者：
Kolek, OI;Hines, ER;Ghishan, FK
通讯作者：
Ghishan, FK
影响因子：
14.9
作者：
Dreszer TR;Karolchik D;Zweig AS;Hinrichs AS;Raney BJ;Kuhn RM;Meyer LR;Wong M;Sloan CA;Rosenbloom KR;Roe G;Rhead B;Pohl A;Malladi VS;Li CH;Learned K;Kirkup V;Hsu F;Harte RA;Guruvadoo L;Goldman M;Giardine BM;Fujita PA;Diekhans M;Cline MS;Clawson H;Barber GP;Haussler D;James Kent W
通讯作者：
James Kent W
影响因子：
5.3
作者：
Kim, Sungtae;Yamazaki, Miwa;Pike, J. Wesley
通讯作者：
Pike, J. Wesley
DOI：
10.1152/ajpendo.00502.2004
发表时间：
2005-06-01
影响因子：
5.1
作者：
Ito, M;Sakai, Y;Miyamoto, K
通讯作者：
Miyamoto, K