Klotho 在慢性肾脏病血管钙化中作用的研究进展

doi:10.3969/j.issn.1671-4091.2021.03.010

中国血液净化 ›› 2021, Vol. 20 ›› Issue (03): 189-192.doi: 10.3969/j.issn.1671-4091.2021.03.010

Klotho 在慢性肾脏病血管钙化中作用的研究进展

杨枫¹,林评兰¹,邹赟¹,叶朝阳¹

1上海中医药大学附属曙光医院肾病科，中医肾病研究所，肝肾疾病病证教育部重点实验室(上海中医药大学)，上海市中医临床重点实验室(14DZ2273200)

收稿日期:2020-10-15 修回日期:2020-12-09 出版日期:2021-03-12 发布日期:2021-03-12
通讯作者: 叶朝阳 yechaoyang63@126.com E-mail:yechaoyan963@126.com
基金资助:
浦东新区中西医结合慢性肾病学科群(PWZxq2017-07)，国家自然科学基金面上项目(81873617)，
上海中医药大学预算内项目(18LK046)，上海市青年科技英才扬帆计划项目(19YF1449800)

Research progress in the role of klotho in vascular calcification in chronic kidney disease

1Department of Nephrology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine; Traditional Chinese Medicine Institute of Kidney Disease, Shanghai University of Traditional Chinese Medicine; Key Laboratory of Liver and Kidney Diseases, Ministry of Education; Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai 201203, China

Received:2020-10-15 Revised:2020-12-09 Online:2021-03-12 Published:2021-03-12
Contact: Chao-yang chaoYe E-mail:yechaoyan963@126.com

摘要/Abstract

摘要： 慢性肾脏病(Chronic Kidney Disease, CKD)发病率逐年升高，慢性肾脏病患者随其肾功能下降并发骨矿物质代谢紊乱，主要表现为钙磷代谢异常、继发性甲状旁腺功能亢进、血管钙化(Vascular calcification, VC)等，导致心血管病变高发及死亡率增加。研究表明，抗衰老基因Klotho主要表达于肾，具有抑制肾纤维化和调节钙磷代谢紊乱等保护肾脏的作用。本文围绕klotho蛋白在VC中的作用最新研究进展进行综述。

关键词: 血管钙化, klotho, FGF23, 慢性肾脏病

Abstract: 【Abstract】The incidence of chronic kidney disease (CKD) is increasing progressively. CKD patients are frequently accompanied with bone mineral metabolism disorder (CKD-MBD) along with the decline of renal function. CKD-MBD is mainly manifested by abnormal calcium and phosphorus metabolism, secondary hyperparathyroidism and vascular calcification (VC), leading to the higher incidence of cardiovascular disease and the negative impacts on quality of life and prognosis of the patients. Recent studies have shown that Klotho is an anti-aging gene, which is mainly expressed in kidney and protects kidney through the inhibition of renal fibrosis and regulation of calcium and phosphorus metabolism. This review focuses on recent research progress in the role of Klotho on VC.

Key words: Vascular calcification, Klotho, FGF23, Chronic kidney disease

中图分类号:

R692.5

杨枫, 林评兰, 邹赟, 叶朝阳. Klotho 在慢性肾脏病血管钙化中作用的研究进展[J]. 中国血液净化, 2021, 20(03): 189-192.

参考文献

[1] Webster AC, Nagler EV, Morton RL, Masson P: Chronic Kidney Disease[J]. Lancet, 2017, 389(10075):1238-1252.
[2] Shroff R, Long DA, Shanahan C. Mechanistic insights into vascular calcification in CKD[J]. J Am Soc Nephrol. 2013;24(2):179-189.
[3] Kurosu H, Ogawa Y, Miyoshi M, Yamamoto M, Nandi A, Rosenblatt KP, Baum MG, Schiavi S, Hu MC, Moe OW, Kuro-o M: Regulation of fibroblast growth factor-23 signaling by klotho[J]. J Biol Chem 2006, 281:6120-6123.
[4] Urakawa I, Yamazaki Y, Shimada T, Iijima K, Hasegawa H, Okawa K, Fujita T, Fukumoto S, Yamashita T: Klotho converts canonical FGF receptor into a specific receptor for FGF23[J]. Nature 2006, 444:770-774.
[5] Hu MC, Shi M, Zhang J, Pastor J, Nakatani T, Lanske B, Razzaque MS, Rosenblatt KP, Baum MG, Kuro-o M, Moe OW: Klotho: a novel phosphaturic substance acting as an autocrine enzyme in the renal proximal tubule[J]. FASEB J 2010, 24:3438-3450.
[6] Wang Y, Sun Z: Klotho gene delivery prevents the progression of spontaneous hypertension and renal damage[J]. Hypertension 2009, 54: 810-817.
[7] Kurosu H, Kuro-o M. The Klotho gene family as a regulator of endocrine fibroblast growth factors[J]. Mol Cell Endocrinol 299:72-78. Molecular & Cellular Endocrinology, 2008, 299(1):72-78.
[8] Sopjani M , Rinnerthaler M , Kruja J , et al. Intracellular Signaling of the Aging Suppressor Protein Klotho[J]. Current Molecular Medicine, 2015, 15(1):27-37.
[9] Kuro-o M. Klotho as a regulator of fibroblast growth factor signaling and phosphate/calcium metabolism.[J]. Current Opinion in Nephrology & Hypertension, 2006, 15(4):437.
[10] Lindberg K, Amin R, Moe OW, et al. The kidney is the principal organ mediating klotho effects[J]. J Am Soc Nephrol. 2014; 25:2169–2175.
[11] Feger M, Mia S, Pakladok T, et al. Down-regulation of renal klotho expression by Shiga toxin 2[J]. Kidney Blood Press Res. 2014; 39:441–449.
[12] Alexander RT, Woudenberg-Vrenken TE, Buurman J, Dijkman H, van der Eerden BC, van Leeuwen JP, Bindels RJ, Hoenderop JG: Klotho prevents renal calcium loss[J]. J Am Soc Nephrol 2009, 20: 2371-2379.
[13] Vervloet M, Cozzolino M. Vascular calcification in chronic kidney disease: different bricks in the wall[J]? Kidney Int. 2017;91(4):808-817.
[14] Lu X, Hu MC. Klotho/FGF23 Axis in Chronic Kidney Disease and Cardiovascular Disease[J]. Kidney Dis (Basel). 2017;3(1):15-23.
[15] Kuro-o M. Klotho in chronic kidney disease--what's new[J]? Nephrol Dial Transplant. 2009;24(6):1705-1708.
[16] 吴明,林评兰,叶朝阳.慢性肾脏病血管钙化的研究进展[J].中国血液净化,2018,17(06):361-365.
[17] Durham AL, Speer MY, Scatena M, Giachelli CM, Shanahan CM. Role of smooth muscle cells in vascular calcification: implications in atherosclerosis and arterial stiffness[J]. Cardiovasc Res. 2018;114(4):590-600.
[18] Kuro-o M, Matsumura Y, Aizawa H, et al. Mutation of the mouse klotho gene leads to a syndrome resembling ageing[J]. Nature. 1997;390(6655):45-51.
[19] 常晋瑞,孙娜,南瑛,于玮,齐永芬.Klotho的研究进展[J].生理科学进展,2015,46(04):245-249.
[20] Ogawa Y, Kurosu H, Yamamoto M, Nandi A, Rosenblatt KP, Goetz R, Eliseenkova AV, Mohammadi M, Kuro-o M. β-Klotho is required for metabolic activity of fibroblast growth factor 21[J]. Proc Natl Acad. 2007;1,104(18):7432-7.
[21] Adams AC, Cheng CC, Coskun T, Kharitonenkov A. FGF21 requires β-klotho to act in vivo. PLoS One. 2012;7(11):e49977.
[22]史雨晨,柳景华.血管钙化大鼠模型肾脏β-Klotho及成纤维细胞生长因子受体1表达研究[J].中国循环杂志,2017,32(05):507-510.
[23]戴厚永,杨斌.Klotho与肾损伤及修复的研究进展[J].生理学报,2018,70(06):639-643.
[24] Yamada S, Giachelli CM. Vascular calcification in CKD-MBD: Roles for phosphate, FGF23, and Klotho[J]. Bone. 2017;100:87-93.
[25] Hu MC, Shi M, Zhang J, et al. Klotho deficiency causes vascular calcification in chronic kidney disease[J]. J Am Soc Nephrol. 2011;22(1):124-136.
[26] Razzaque MS. The FGF23-Klotho axis: endocrine regulation of phosphate homeostasis[J]. Nat Rev Endocrinol. 2009;5(11):611-619.
[27] Lu X, Hu MC. Klotho/FGF23 Axis in Chronic Kidney Disease and Cardiovascular Disease[J]. Kidney Dis (Basel). 2017;3(1):15-23.
[28]马春园,郝丽荣.FGF23-Klotho轴在慢性肾脏病骨矿物质代谢紊乱中的作用[J].医学综述,2015,21(07):1169-1172.
[29] Chen T, Mao H, Chen C, et al. The Role and Mechanism of α-Klotho in the Calcification of Rat Aortic Vascular Smooth Muscle Cells[J]. Biomed Res Int. 2015;2015:194362.
[30] Lim K, Lu TS, Molostvov G, et al. Vascular Klotho deficiency potentiates the development of human artery calcification and mediates resistance to fibroblast growth factor 23[J]. Circulation. 2012;125(18):2243-2255.
[31] Hum JM, O'Bryan LM, Tatiparthi AK, et al. Chronic Hyperphosphatemia and Vascular Calcification Are Reduced by Stable Delivery of Soluble Klotho[J]. J Am Soc Nephrol. 2017;28(4):1162-1174.
[32] Hu MC. Klotho connects intermedin1-53 to suppression of vascular calcification in chronic kidney disease[J]. Kidney Int. 2016;89(3):534-537.
[33] Zhao Y, Zhao MM, Cai Y, et al. Mammalian target of rapamycin signaling inhibition ameliorates vascular calcification via Klotho upregulation[J]. Kidney Int. 2015;88(4):711-721.
[34] Doi S, Zou Y, Togao O, Pastor JV, John GB, Wang L, Shiizaki K, Gotschall R, Schiavi S, Yorioka N, Takahashi M, Boothman DA, Kuro-o M: Klotho inhibits transforming growth factor- beta1 (TGF-beta1) signaling and suppresses renal fibrosis and cancer metastasis in mice[J]. J Biol Chem. 2011; 286: 8655–8665.
[35] Satoh M , Nagasu H , Morita Y , et al. Klotho protects against mouse renal fibrosis by inhibiting Wnt signaling[J]. Am J of Physiol, 2012; 303(12):F1641-F1651.
[36] Hu MC , Shi M , Zhang J , et al.Klotho deficiency is an early biomarker of renal ischemia-reperfusion injury and its replacement is protective[J]. Kidney Int. 2010; 78:1240–1251.
[37] Drew D, Kritchevsky S, Ix J, Shlipak M, Gutie?rrez OM, Newman A, Hoofnagle A, Fried L, Semba RD, Sarnak M. Association between soluble Klotho and change in kidney function: the health aging and body composition study[J]. J Am Soc Nephro. 2017; l28:1859–1866.
[38] Azuma M , Koyama D , Kikuchi J , et al. Promoter methylation confers kidney-specific expression of the Klotho gene[J]. Faseb J. 2012; 26(10):4264-74.
[39] Liu S, Tang W, Zhou J, et al. Fibroblast growth factor 23 is a counter-regulatory phosphaturic hormone for vitamin D. J Am Soc Nephrol. 2006; 17(5):1305–1315.
[40] Lau WL,Leaf EM,Hu MC,et al.Vitamin D receptor agonists increase klotho and osteopontin while decreasing aortic calcification in mice with chronic kidney disease fed a high phosphate diet[J].Kidney Int,2012,82(12):1261-1270.
[41] Durham AL, Speer MY, Scatena M, Giachelli CM, Shanahan CM. Role of smooth muscle cells in vascular calcification: implications in atherosclerosis and arterial stiffness[J]. Cardiovasc Res. 2018, 114(4):590–600.
[42] Yamamoto M, Clark JD, Pastor JV, et al. Regulation of oxidative stress by the anti-aging hormone klotho[J]. J Biol Chem. 2005; 280(45):38029–38034.

Klotho 在慢性肾脏病血管钙化中作用的研究进展

Research progress in the role of klotho in vascular calcification in chronic kidney disease

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