摘要
肾主水是指肾脏可通过其对水液的排泄以及重吸收功能调节全身水液代谢。通过将成纤维细胞生长因子(Fibroblast growth factor,FGF23)的调磷特性与肾主水的理论机制进行关联性分析,探讨FGF23在肾主水过程中的作用机制。FGF23是由骨细胞或成骨细胞分泌的一种内分泌激素,通过与肾脏表明的Klotho蛋白相结合,调节肾小管上皮细胞对于磷酸盐的重吸收,进而达到体内磷代谢的调节。因此,FGF23参与肾主水的整个重吸收的生理过程。
The" " kidney governing" water means that the kidney can regulate the metabolism of whole body water through its excretion and reabsorption function of water.The mechanism of FGF23 in the process of " kidney governing water" was discussed by analyzing the relationship between FGF23's phosphorus regulating characteristics and the mechanism of " kidney governing water".FGF23 is an endocrine hormone secreted by osteoblasts or osteoblasts that regulates the reabsorption of phosphate by the renal tubular epithelial cells through combining with the Klotho protein expressed in the kidney to regulate the metabolism of phosphorus in the body.Therefore,FGF23 participates in the physiological process of kidney reabsorption.
引文
[1]张淑婧.浅述"肾主水"之内涵及作用机制[J].世界最新医学信息文摘,2017,17(45):40.
[2]Urakawa I,Yamazaki Y,Shimada T,et al.Klotho converts canonical FGF receptor into a specific receptor for FGF23[J].Nature,2006,444(7120):770.
[3]Yamashita T,Yoshioka M,Itoh N.Identification of a Novel Fibroblast Growth Factor,FGF-23,Preferentially Expressed in the Ventrolateral Thalamic Nucleus of the Brain[J].Biochemical&Biophysical Research Communications,2000,277(2):494.
[4]Consortium A.Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23[J].Nature Genetics,2000,26(3):345.
[5]White K E,Jonsson K B,Carn G,et al.The Autosomal Dominant Hypophosphatemic Rickets(ADHR)Gene Is a Secreted Polypeptide Overexpressed by Tumors that Cause Phosphate Wasting[J].J Clin Endocrinol Metab,2001,86(2):497.
[6]Shimada T,Mizutani S,Muto T,et al.Cloning and characterization of FGF23 as a causative factor of tumor-induced osteomalacia[J].Proc Natl Acad Sci U S A,2001,98(11):6500.
[7]Shimada T,Muto T,Urakawa I,et al.Mutant FGF-23 Responsible for Autosomal Dominant Hypophosphatemic Rickets Is Resistant to Proteolytic Cleavage and Causes Hypophosphatemia in Vivo[J].Endocrinology,2002,143(8):3179.
[8]White K E,Carn G,Lorenzdepiereux B,et al.Autosomal-dominant hypophosphatemic rickets(ADHR)mutations stabilize FGF-23[J].Kidney International,2001,60(6):2079.
[9]Consortium A.Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23[J].Nature Genetics,2000,26(3):345.
[10]Goetz R,Beenken A,Ibrahimi O A,et al.Molecular insights into the klotho-dependent,endocrine mode of action of fibroblast growth factor19 subfamily members[J].Molecular&Cellular Biology,2007,27(9):3417.
[11]Van B G,Ruinemans-Koerts J,Joosten F,et al.Tumor producing fibroblast growth factor 23 localized by two-staged venous sampling[J].European Journal of Endocrinology,2008,158(3):431.
[12]Shimada T,Urakawa I,Yamazaki Y,et al.FGF-23 transgenic mice demonstrate hypophosphatemic rickets with reduced expression of sodium phosphate cotransporter type IIa[J].Biochemical&Biophysical Research Communications,2004,314(2):409.
[13]Shimada T,Kakitani M,Yamazaki Y,et al.Targeted ablation of Fgf23demonstrates an essential physiological role of FGF23 in phosphate and vitamin D metabolism[J].Journal of Clinical Investigation,2004,113(4):561.
[14]Gattineni J,Bates C,Twombley K,et al.FGF23 decreases renal Na Pi-2a and Na Pi-2c expression and induces hypophosphatemia in vivo predominantly via FGF receptor 1[J].American Journal of Physiology-Renal Physiology,2009,297(2):F282.
[15]Lemmon M A,Schlessinger J.Cell signaling by receptor tyrosine kinases[J].Cell,2010,141(7):1117.
[16]Goetz R,Beenken A,Ibrahimi O A,et al.Molecular insights into the klotho-dependent,endocrine mode of action of fibroblast growth factor19 subfamily members[J].Molecular&Cellular Biology,2007,27(9):3417.
[17]Urakawa I,Yamazaki Y,Shimada T,et al.Klotho converts canonical FGF receptor into a specific receptor for FGF23[J].Nature,2006,444(7120):770.
[18]Kurosu H,Ogawa Y,Miyoshi M,et al.Regulation of fibroblast growth factor-23 signaling by klotho[J].Journal of Biological Chemistry,2006,281(10):6120.
[19]Goetz R,Ohnishi M,Ding X,et al.Klotho coreceptors inhibit signaling by paracrine fibroblast growth factor 8 subfamily ligands[J].Molecular&Cellular Biology,2012,32(10):1944.
[20]Chen G,Liu Y,Goetz R,et al.α-Klotho is a non-enzymatic molecular scaffold for FGF23 hormone signalling[J].Nature,2018,553(7689):481.
[21]Nabeshima Y,Imura H.α-Klotho:A Regulator That Integrates Calcium Homeostasis[J].American Journal of Nephrology,2008,28(3):455.
[22]Andrukhova O,Zeitz U,Goetz R,et al.FGF23 acts directly on renal proximal tubules to induce phosphaturia through activation of the ERK1/2-SGK1 signaling pathway[J].Bone,2012,51(3):621.
[23]Baum M,Schiavi S,Dwarakanath V,et al.Effect of fibroblast growth factor-23 on phosphate transport in proximal tubules[J].Kidney International,2005,68(3):1148.
[24]Perwad F,Zhang M Y,Tenenhouse H S,et al.Fibroblast growth factor 23 impairs phosphorus and vitamin D metabolism in vivo and suppresses 25-hydroxyvitamin D-1alpha-hydroxylase expression in vitro[J].Am J Physiol Renal Physiol,2007,293(5):F1577.
[25]Larsson T,Marsell R,Schipani E,et al.Transgenic mice expressing Fibroblast Growth Factor-23 under the control of theα1(I)collagen promoter exhibit growth retardation,Osteomalacia and disturbed phosphate homeostasis[J].Endocrinology,2004,145(7):3087.
[26]Saito H,Kusano K,Kinosaki M,等.Human fibroblast growth factor-23 mutants suppress Na+-dependent phosphate co-transport activity and 1alpha,25-dihydroxyvitamin D3 production[J].Journal of Biological Chemistry,2003,278(4):2206.
[27]Inoue Y,Segawa H,Kaneko I,et al.Role of the vitamin D receptor in FGF23 action on phosphate metabolism[J].Biochemical Journal,2005,390(1):325-331.
[28]Kuroo M.Phosphate and Klotho[J].Kidney International,2011,79(121):S20.
[29]王剑,郑洪新,杨芳.“肾藏精”藏象理论探析[J].中国中医基础医学杂志,2011,17(02):119.
[30]黄和贤,曹文富.“肾主水”与肾病性水代谢紊乱及肾水通道蛋白2关系探讨[J].实用中医药杂志,2011,27(12):870.
[31]叶海丰,莫芳芳,张国霞.“肾主水”理论及临床研究进展[J].时珍国医国药,2010,21(7):1842.
[32]Kurosu H,Yamamoto M,Clark J D,et al.Suppression of aging in mice by the hormone Klotho[J].Science,2005,309(5742):1829.
[33]Hu M C,Kuroo M,Moe O W.The emerging role of Klotho in clinical nephrology[J].Nephrology,dialysis,transplantation:official publication of the European Dialysis and Transplant Association-European Renal Association,2012,27(7):2650.
[34]Martin A,David V,Quarles L D.Regulation and function of the FGF23/klotho endocrine pathways[J].Physiological Reviews,2012,92(1):131.
