The nuclear vitamin D receptor controls the expression of genes encoding factors which feed the "Fountain of Youth" to mediate healthful aging.
The nuclear vitamin D receptor controls the expression of genes encoding factors which feed the "Fountain of Youth" to mediate healthful aging.
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DOI：
10.1016/j.jsbmb.2010.03.019
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发表时间：
2010-07
影响因子：
4.1
通讯作者：
Jurutka, Peter W.
中科院分区：
文献类型：
--
作者：
Haussler, Mark R.;Haussler, Carol A.;Whitfield, G. Kerr;Hsieh, Jui-Cheng;Thompson, Paul D.;Barthel, Thomas K.;Bartik, Leonid;Egan, Jan B.;Wu, Yifei;Kubicek, Jana L.;Lowmiller, Christine L.;Moffet, Eric W.;Forster, Ryan E.;Jurutka, Peter W.
关键词：
核维生素D受体（VDR）结合其高亲和力肾内分泌配体1，25-二羟基维生素D3（1，25 D），以发出肠钙和磷酸盐吸收以及骨重建的信号，产生无佝偻病/骨软化的矿化骨骼，降低了骨质疏松性骨折的风险。1，25 D/VDR信号调节TRPV 6、BGP、SPP 1、LRP 5、RANKL和OPG的表达，同时通过调控CYP 24 A1、PTH、FGF 23、PHEX和klotho转录实现矿物离子的反馈控制，以防止年龄相关性异位钙化。当循环25-羟基维生素D3（反映维生素D状态的代谢物）通过肾外CYP 27 B1局部转化为1，25 D并结合VDR以促进免疫调节、抗微生物防御、异生物质解毒、抗炎/抗癌作用和心血管益处时，维生素D还发挥多种内分泌作用。VDR还通过与β-连环蛋白的直接相互作用影响Wnt信号传导，配体依赖性地钝化结肠癌细胞中β-连环蛋白介导的转录以减弱生长，同时通过成骨细胞和角质形成细胞中的VDR配体非依赖性机制增强β-连环蛋白信号传导以分别发挥成骨作用和作为促毛发循环受体。最后，VDR还通过抑制SOSTDC 1、S100 A8/S100 A9和PTHrP与无毛辅阻遏物一起驱动哺乳动物毛发周期。毛发为陆地哺乳动物提供了抵御紫外线引起的皮肤损伤和癌症的屏障，阐明了VDR促进健康衰老的另一个功能。
The nuclear vitamin D receptor (VDR) binds 1,25-dihydroxyvitamin D3 (1,25D), its high affinity renal endocrine ligand, to signal intestinal calcium and phosphate absorption plus bone remodeling, generating a mineralized skeleton free of rickets/osteomalacia with a reduced risk of osteoporotic fractures. 1,25D/VDR signaling regulates the expression of TRPV6, BGP, SPP1, LRP5, RANKL and OPG, while achieving feedback control of mineral ions to prevent age-related ectopic calcification by governing CYP24A1, PTH, FGF23, PHEX, and klotho transcription. Vitamin D also elicits numerous intracrine actions when circulating 25-hydroxyvitamin D3, the metabolite reflecting vitamin D status, is converted to 1,25D locally by extrarenal CYP27B1, and binds VDR to promote immunoregulation, antimicrobial defense, xenobiotic detoxification, anti-inflammatory/anticancer actions and cardiovascular benefits. VDR also affects Wnt signaling through direct interaction with β-catenin, ligand-dependently blunting β-catenin mediated transcription in colon cancer cells to attenuate growth, while potentiating β-catenin signaling via VDR ligand-independent mechanisms in osteoblasts and keratinocytes to function osteogenically and as a pro-hair cycling receptor, respectively. Finally, VDR also drives the mammalian hair cycle in conjunction with the hairless corepressor by repressing SOSTDC1, S100A8/S100A9, and PTHrP. Hair provides a shield against UV-induced skin damage and cancer in terrestrial mammals, illuminating another function of VDR that facilitates healthful aging.
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影响因子：
6.5
作者：
Ellison, Tara I.;Smith, Molly K.;MacDonald, Paul N.
通讯作者：
MacDonald, Paul N.
DOI：
10.1016/j.bbrc.2006.12.011
发表时间：
2007-02-02
影响因子：
3.1
作者：
Fukuda, Toru;Kanomata, Kazuhiro;Katagiri, Takenobu
通讯作者：
Katagiri, Takenobu
影响因子：
4.8
作者：
Dardenne, O;Prud'homme, J;St-Arnaud, R
通讯作者：
St-Arnaud, R
影响因子：
6.1
作者：
Haussler, Mark R.;Haussler, Carol A.;Jurutka, Peter W.
通讯作者：
Jurutka, Peter W.
DOI：
10.1196/annals.1402.070
发表时间：
2007-01-01
期刊：
SKELETAL BIOLOGY AND MEDICINE, PT A
影响因子：
--
作者：
Christakos, Sylvia;Dhawan, Puneet;Joshi, Sneha
通讯作者：
Joshi, Sneha