[1]杜娟,夏维波.成纤维细胞生长因子-23的代谢调控及与疾病的关系[J].国际内分泌代谢杂志,2017,37(02):123-127.[doi:10.3760/cma.j.issn.1673-4157.2017.02.014]
　Du Juan,Xia Weibo..The metabolic regulation of fibroblast growth factor-23 and its relation with diseases[J].International Journal of Endocrinology and Metabolism,2017,37(02):123-127.[doi:10.3760/cma.j.issn.1673-4157.2017.02.014]
点击复制

成纤维细胞生长因子-23的代谢调控及与疾病的关系()
分享到：

《国际内分泌代谢杂志》[ISSN:1673-4157/CN:12-1383/R]

卷:
37
期数:
2017年02期
页码:
123-127
栏目:
综述
出版日期:
2017-03-20

文章信息/Info

Title:
The metabolic regulation of fibroblast growth factor-23 and its relation with diseases
作者:
杜娟; 夏维波
100730 北京,中国医学科学院,北京协和医学院,北京协和医院内分泌科,国家卫生和计划生育委员会内分泌重点实验室
Author(s):
Du Juan;  Xia Weibo.
Department of Endocrinology, Key Laboratory of Endocrinology, National Health and Family Planning Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing
关键词:
成纤维细胞生长因子-23;  Klotho;  磷代谢;  慢性肾脏疾病;  心血管疾病
Keywords:
Fibroblast growth factor-23;  Klotho;  Phosphate homeostasis;  Chronic kidney disease;  Cardiovascular disease
DOI:
10.3760/cma.j.issn.1673-4157.2017.02.014
摘要:
成纤维细胞生长因子-23(FGF-23)是一种重要的骨源性调磷激素,其主要受体为成纤维细胞生长因子受体(FGFR)/Klotho复合物。多种因素共同参与FGF-23的生理及病理性调控。FGF-23的主要生理作用为调节磷和维生素D代谢。FGF-23的代谢耦联失衡可导致多种磷代谢异常疾病,如X连锁遗传性低血磷性佝偻病、常染色体显性遗传性低血磷性佝偻病、常染色体隐性遗传性低血磷性佝偻病和肿瘤性骨软化症等。随着研究的深入,已明确高水平的FGF-23在慢性肾脏疾病和心血管疾病中发挥重要的病理作用,其精确的调控网络及分子机制仍有待阐明。此外,新近的研究已初步探讨了FGF-23在糖、脂代谢中的作用。
Abstract:
Fibroblast growth factor(FGF)-23 is a bone-derived hormone that is mainly binded to FGF receptor/Klotho combination. Numerous factors have been implicated in the physiological and pathological regulation of FGF-23 expression. FGF-23 has been originally shown to function as a central regulator of phosphate and vitamin D metabolism. Disruption of FGF-23 in metabolic homeostasis plays a significant role in the pathogenesis of phosphate-associated diseases, including X-link dominate hypophosphatemic rickets, autosomal dominant hypophosphatemic rickets, autosomal recessive hypophosphatemic rickets and tumor-induced osteomalacia. Accompanied with further studies, high level of FGF-23 is pathologically involved in the development of chronic kidney disease and cardiovascular disease. The precise metabolic regulation and molecular mechanisms of FGF-23 underlying these conditions remain to be elucidated. Moreover, the emerging roles of FGF-23 in glucose and lipid metabolism have been investigated.

参考文献/References:

[1] Carpenter TO. The expanding family of hypophosphatemic syndromes[J].J Bone Miner Metab,2012,30(1):1-9. DOI: 10.1007/s00774-011-0340-2.
[2] Andrukhova O, Slavic S, Smorodchenko A,et al. FGF23 regulates renal sodium handling and blood pressure[J].EMBO Mol Med,2014,6(6):744-759. DOI: 10.1002/emmm.201303716.
[3] Faul C, Amaral AP, Oskouei B,et al. FGF23 induces left ventricular hypertrophy[J].J Clin Invest,2011,121(11):4393-4408. DOI: 10.1172/JCI46122.
[4] Hu MC, Shiizaki K, Kuro-o M,et al. Fibroblast growth factor 23 and Klotho: physiology and pathophysiology of an endocrine network of mineral metabolism[J].Annu Rev Physiol,2013,75:503-533. DOI: 10.1146/annurev-physiol-030212-183727.
[5] Xu Y, Sun Z. Molecular basis of Klotho: from gene to function in aging[J].Endocr Rev,2015,36(2):174-193.DOI:10.1210/er.2013-1079.
[6] Razzaque MS. The role of Klotho in energy metabolism[J]. Nat Rev Endocrinol,2012,8(10):579-587. DOI: 10.1038/nrendo.2012.75.
[7] Takenaka T, Inoue T, Miyazaki T,et al. Xeno-klotho inhibits parathyroid hormone signaling[J].J Bone Miner Res,2016,31(2):455-462.DOI:10.1002/jbmr.2691.
[8] Collins MT, Lindsay JR, Jain A,et al. Fibroblast growth factor-23 is regulated by 1alpha,25-dihydroxyvitamin D[J].J Bone Miner Res,2005,20(11):1944-1950.
[9] Perwad F, Azam N, Zhang MY,et al. Dietary and serum phosphorus regulate fibroblast growth factor 23 expression and 1,25-dihydroxyvitamin D metabolism in mice[J].Endocrinology,2005,146(12):5358-5364. DOI:10.1210/en.2005-0777.
[10] Scanni R, vonRotz M, Jehle S,et al. The human response to acute enteral and parenteral phosphate loads[J].J Am Soc Nephrol,2014,25(12):2730-2739.DOI:10.1681/ASN.2013101076.
[11] Meir T, Durlacher K, Pan Z,et al. Parathyroid hormone activates the orphan nuclear receptor Nurr1 to induce FGF23 transcription[J].Kidney Int,2014,86(6):1106-1115. DOI: 10.1038/ki.2014.215.
[12] Fan Y, Bi R, Densmore MJ,et al. Parathyroid hormone 1 receptor is essential to induce FGF23 production and maintain systemic mineral ion homeostasis[J].FASEB J,2016,30(1):428-440. DOI: 10.1096/fj.15-278184.
[13] Lavi-Moshayoff V, Wasserman G, Meir T,et al. PTH increases FGF23 gene expression and mediates the high-FGF23 levels of experimental kidney failure: a bone parathyroid feedback loop[J].Am J Physiol Renal Physiol,2010,299(4):F882-F889. DOI: 10.1152/ajprenal.00360.2010.
[14] Tebben PJ, Singh RJ, Clarke BL,et al. Fibroblast growth factor 23, parathyroid hormone, and 1alpha,25-dihydroxyvitamin D in surgically treated primary hyperparathyroidism[J].Mayo Clin Proc,2004,79(12):1508-1513.
[15] David V, Martin A, Isakova T, et al. Inflammation and functional iron deficiency regulate fibroblast growth factor 23 production[J].Kidney Int,2016,89(1):135-146.DOI:10.1038/ki.2015.290.
[16] Wolf M, Koch TA, Bregman DB. Effects of iron deficiency anemia and its treatment on fibroblast growth factor 23 and phosphate homeostasis in women[J].J Bone Miner Res,2013,28(8):1793-1803. DOI: 10.1002/jbmr.1923.
[17] Kawai M, Kinoshita S, Shimba S,et al. Sympathetic activation induces skeletal Fgf23 expression in a circadian rhythm-dependent manner[J].J Biol Chem,2014,289(3):1457-1466. DOI: 10.1074/jbc.M113.500850.
[18] Xiao Z, Huang J, Cao L,et al. Osteocyte-specific deletion of Fgfr1 suppresses FGF23[J].PLoS One,2014,9(8):e104154. DOI: 10.1371/journal.pone.0104154.
[19] Han X, Xiao Z, Quarles LD. Membrane and integrative nuclear fibroblastic growth factor receptor(FGFR)regulation of FGF-23[J].J Biol Chem,2015,290(33):20101. DOI: 10.1074/jbc.A114.609230.
[20] Carpenter TO, Imel EA, Ruppe MD,et al. Randomized trial of the anti-FGF23 antibody KRN23 in X-linked hypophosphatemia[J].J Clin Invest,2014,124(4):1587-1597. DOI: 10.1172/JCI72829.
[21] Zhang X, Imel EA, Ruppe MD,et al. Pharmacokinetics and pharmacodynamics of a human monoclonal anti-FGF23 antibody(KRN23)in the first multiple ascending-dose trial treating adults with X-linked hypophosphatemia[J].J Clin Pharmacol,2016,56(2):176-185. DOI: 10.1002/jcph.570.
[22] Farrow EG, Yu X, Summers LJ,et al. Iron deficiency drives an autosomal dominant hypophosphatemic rickets(ADHR)phenotype in fibroblast growth factor-23(Fgf23)knock-in mice[J].Proc Natl Acad Sci U S A,2011,108(46):E1146-E1155. DOI: 10.1073/pnas.1110905108.
[23] Kapelari K, Köhle J, Kotzot D, et al. Iron supplementation associated with loss of phenotype in autosomal dominant hypophosphatemic rickets[J].J Clin Endocrinol Metab,2015,100(9):3388-3392. DOI: 10.1210/jc.2015-2391.
[24] Mackenzie NC, Huesa C, Rutsch F,et al. New insights into NPP1 function: lessons from clinical and animal studies[J].Bone,2012,51(5):961-968. DOI: 10.1016/j.bone.2012.07.014.
[25] Lee JC, Jeng YM, Su SY,et al. Identification of a novel FN1-FGFR1 genetic fusion as a frequent event in phosphaturic mesenchymal tumour[J].J Pathol,2015,235(4):539-545. DOI: 10.1002/path.4465.
[26] Ix JH, Katz R, Kestenbaum BR,et al. Fibroblast growth factor-23 and death, heart failure, and cardiovascular events in community-living individuals: CHS(Cardiovascular Health Study)[J].J Am Coll Cardiol,2012,60(3):200-207. DOI: 10.1016/j.jacc.2012.03.040.
[27] Isakova T, Xie H, Yang W,et al. Fibroblast growth factor 23 and risks of mortality and end-stage renal disease in patients with chronic kidney disease[J].JAMA,2011,305(23):2432-2439. DOI: 10.1001/jama.2011.826.
[28] Isakova T, Wahl P, Vargas GS,et al. Fibroblast growth factor 23 is elevated before parathyroid hormone and phosphate in chronic kidney disease[J].Kidney Int,2011,79(12):1370-1378. DOI: 10.1038/ki.2011.47.
[29] Christov M, Waikar SS, Pereira RC,et al. Plasma FGF23 levels increase rapidly after acute kidney injury[J].Kidney Int,2013,84(4):776-785. DOI: 10.1038/ki.2013.150.
[30] Umanath K, Sika M, Niecestro R,et al. Rationale and study design of a three-period, 58-week trial of ferric citrate as a phosphate binder in patients with ESRD on dialysis[J].Hemodial Int,2013,17(1):67-74. DOI: 10.1111/j.1542-4758.2012.00711.x.
[31] Kendrick J, Cheung AK, Kaufman JS,et al. FGF-23 associates with death, cardiovascular events, and initiation of chronic dialysis[J].J Am Soc Nephrol,2011,22(10):1913-1922. DOI: 10.1681/ASN.2010121224.
[32] Faul C, Amaral AP, Oskouei B,et al. FGF23 induces left ventricular hypertrophy[J].J Clin Invest,2011,121(11):4393-4408. DOI: 10.1172/JCI46122.
[33] Grabner A, Amaral AP, Schramm K,et al. Activation of cardiac fibroblast growth factor receptor 4 causes left ventricular hypertrophy[J].Cell Metab,2015,22(6):1020-1032. DOI: 10.1016/j.cmet.2015.09.002.
[34] Andrukhova O, Slavic S, Odörfer KI,et al. Experimental myocardial infarction upregulates circulating fibroblast growth factor-23[J].J Bone Miner Res,2015,30(10):1831-1839. DOI: 10.1002/jbmr.2527.
[35] Semba RD, Cappola AR, Sun K,et al. Plasma klotho and cardiovascular disease in adults[J].J Am Geriatr Soc,2011,59(9):1596-1601. DOI: 10.1111/j.1532-5415.2011.03558.x.
[36] Xie J, Cha SK, An SW,et al. Cardioprotection by Klotho through downregulation of TRPC6 channels in the mouse heart[J].Nat Commun,2012,3:1238. DOI: 10.1038/ncomms2240.
[37] Mirza MA, Alsi J, Hammarstedt A,et al. Circulating fibroblast growth factor-23 is associated with fat mass and dyslipidemia in two independent cohorts of elderly individuals[J].Arterioscler Thromb Vasc Biol,2011,31(1):219-227. DOI: 10.1161/ATVBAHA.110.214619.
[38] Wojcik M, Dolezal-Oltarzewska K, Janus D,et al. FGF23 contributes to insulin sensitivity in obese adolescents - preliminary results[J].Clin Endocrinol(Oxf),2012,77(4):537-540. DOI: 10.1111/j.1365-2265.2011.04299.x.
[39] Wojcik M, Janus D, Dolezal-Oltarzewska K,et al. The association of FGF23 levels in obese adolescents with insulin sensitivity[J].J Pediatr Endocrinol Metab,2012,25(7-8):687-690. DOI:10.1515/jpem-2012-0064.
[40] Garland JS, Holden RM, Ross R,et al. Insulin resistance is associated with fibroblast growth factor-23 in stage 3-5 chronic kidney disease patients[J].J Diabetes Complications,2014,28(1):61-65. DOI: 10.1016/j.jdiacomp.2013.09.004.
[41] Mirza MA, Alsi J, Hammarstedt A,et al. Circulating fibroblast growth factor-23 is associated with fat mass and dyslipidemia in two independent cohorts of elderly individuals[J].Arterioscler Thromb Vasc Biol,2011,31(1):219-227. DOI: 10.1161/ATVBAHA.110.214619.

相似文献/References:

[1]梁珊珊 刘昊凌 高昕媛 辛玉晶.2型糖尿病合并下肢动脉疾病患者血清 FGF-23与骨钙素的关系研究[J].国际内分泌代谢杂志,2020,40(01):10.[doi:DOI:10.3760/cma.j.issn.1673-4157.2020.01.003]
　Liang Shanshan,Liu Haoling,Cao Xinyuan,et al.Relationship between serum FGF-23 and osteocalcin in patients with type 2 diabetes mellitus complicated with lower extremity arterial disease[J].International Journal of Endocrinology and Metabolism,2020,40(02):10.[doi:DOI:10.3760/cma.j.issn.1673-4157.2020.01.003]

备注/Memo

备注/Memo:
通信作者:夏维波,Email:xiaweibo@medmail.com.cn
更新日期/Last Update: 2017-03-20