切换至 "中华医学电子期刊资源库"

中华肾病研究电子杂志 ›› 2021, Vol. 10 ›› Issue (05) : 288 -291. doi: 10.3877/cma.j.issn.2095-3216.2021.05.010

综述

HIF-1α在慢性肾脏病中的研究进展
王东1, 倪洁1,()   
  1. 1. 150081 哈尔滨医科大学附属第一医院肾内科
  • 收稿日期:2021-05-25 出版日期:2021-10-20
  • 通信作者: 倪洁
  • 基金资助:
    黑龙江省自然科学基金(LH2019H025)

Progress of research on HIF-1α in chronic kidney disease

Dong Wang1, Jie Ni1,()   

  1. 1. Department of Nephrology, First Hospital Affiliated to Harbin Medical University, Harbin 150081, Heilongjiang Province, China
  • Received:2021-05-25 Published:2021-10-20
  • Corresponding author: Jie Ni
引用本文:

王东, 倪洁. HIF-1α在慢性肾脏病中的研究进展[J/OL]. 中华肾病研究电子杂志, 2021, 10(05): 288-291.

Dong Wang, Jie Ni. Progress of research on HIF-1α in chronic kidney disease[J/OL]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2021, 10(05): 288-291.

低氧反应与慢性肾脏病(CKD)密切相关,低氧诱导因子(HIF)是机体适应低氧反应的主要调节因子。HIF-1α是HIF的氧敏感性亚基,在CKD发生和发展过程中发挥重要作用。本文就HIF-1α与CKD的炎症、贫血及矿物质与骨异常等的相关性研究作一总结,为进一步研究提供依据。

Hypoxia response is closely related to chronic kidney disease (CKD). Hypoxia-inducible factor (HIF) is the main regulator of the body′s adaptation to hypoxia. HIF-1α is an oxygen-sensitive subunit of HIF, and plays an important role in the occurrence and development of CKD. This article summarized the researches on the correlation between HIF-1α and CKD′s inflammation, anemia, or mineral and bone disorders, etc, in order to provide basis for further study.

图1 HIF-1α参与CKD炎症反应的相关调控机制
[1]
Movafagh S, Raj D, Sanaei-Ardekani M, et al. Hypoxia inducible factor 1: a urinary biomarker of kidney disease [J]. Clin Transl Sci, 2017, 10(3): 201-207.
[2]
Ke Q, Costa M. Hypoxia-inducible factor-1 (HIF-1) [J]. Mol Pharmacol, 2006, 70(5): 1469-1480.
[3]
Liu M, Liu L, Bai M, et al. Hypoxia-induced activation of Twist/miR-214/E-cadherin axis promotes renal tubular epithelial cell mesenchymal transition and renal fibrosis [J]. Biochem Biophys Res Commun, 2018, 495(3): 2324-2330.
[4]
Wei X, Zhu X, Jiang L, et al. Recent advances in understanding the role of hypoxia-inducible factor 1α in renal fibrosis [J]. Int Urol Nephrol, 2020, 52(7): 1287-1295.
[5]
Li X, Chen W, Feng J, et al. The effects of HIF-1α overexpression on renal injury, immune disorders and mitochondrial apoptotic pathways in renal ischemia/reperfusion rats [J]. Transl Androl Urol, 2020, 9(5): 2157-2165.
[6]
Kang MK, Kim SI, Oh SY, et al. Tangeretin ameliorates glucose-induced podocyte injury through blocking epithelial to mesenchymal transition caused by oxidative stress and hypoxia [J]. Int J Mol Sci, 2020, 21(22): 8577.
[7]
Liu G, He L. Salidroside attenuates adriamycin-induced focal segmental glomerulosclerosis by inhibiting the hypoxia-inducible factor-1α expression through phosphatidylinositol 3-kinase/protein kinase B pathway [J]. Nephron, 2019, 142(3): 243-252.
[8]
端爱萍,杨敬平. 缺氧诱导因子与肾脏疾病[J]. 肾脏病与透析肾移植杂志2018, 27(2): 157-160.
[9]
Huang H, Fan Y, Gao Z, et al. HIF-1α contributes to Ang II-induced inflammatory cytokine production in podocytes [J]. BMC Pharmacol Toxicol, 2019, 20(1): 59.
[10]
Henze LA, Luong TTD, Boehme B, et al. Impact of C-reactive protein on osteo-/chondrogenic transdifferentiation and calcification of vascular smooth muscle cells [J]. Aging (Albany NY), 2019, 11(15): 5445-5462.
[11]
Kapitsinou PP, Liu Q, Unger TL, et al. Hepatic HIF-2 regulates erythropoietic responses to hypoxia in renal anemia [J]. Blood, 2010, 116(16): 3039-3048.
[12]
Hirota K. HIF-α prolyl hydroxylase inhibitors and their implications for biomedicine: a comprehensive review [J]. Biomedicines, 2021, 9(5): 468.
[13]
Yeh TL, Leissing TM, Abboud MI, et al. Molecular and cellular mechanisms of HIF prolyl hydroxylase inhibitors in clinical trials [J]. Chem Sci, 2017, 8(11): 7651-7668.
[14]
Yan Z, Xu G. A novel choice to correct inflammation-induced anemia in CKD: oral hypoxia-inducible factor prolyl hydroxylase inhibitor roxadustat [J]. Front Med (Lausanne), 2020, 7: 393.
[15]
Wu K, Zhou K, Wang Y, et al. Stabilization of HIF-1α by FG-4592 promotes functional recovery and neural protection in experimental spinal cord injury [J]. Brain Res, 2016, 1632: 19-26.
[16]
Yu Y, Zhou Y, Cheng T, et al. Hypoxia enhances tenocyte differentiation of adipose-derived mesenchymal stem cells by inducing hypoxia-inducible factor-1α in a co-culture system [J]. Cell Prolif, 2016, 49(2): 173-184.
[17]
Yang R, Zhu Y, Wang Y, et al. HIF-1α/PDK4/autophagy pathway protects against advanced glycation end-products induced vascular smooth muscle cell calcification [J]. Biochem Biophys Res Commun, 2019, 517(3): 470-476.
[18]
Wu X, Zhao Q, Chen Z, et al. Estrogen inhibits vascular calcification in rats via hypoxia-induced factor-1α signaling [J]. Vascular, 2020, 28(4): 465-474.
[19]
Paloian NJ, Giachelli CM. A current understanding of vascular calcification in CKD [J]. Am J Physiol Renal Physiol, 2014, 307(8): F891-F900.
[20]
Mokas S, Larivière R, Lamalice L, et al. Hypoxia-inducible factor-1 plays a role in phosphate-induced vascular smooth muscle cell calcification [J]. Kidney Int, 2016, 90(3): 598-609.
[21]
Nagy A, Pethö D, Gáll T, et al. Zinc inhibits HIF-prolyl hydroxylase inhibitor-aggravated VSMC calcification induced by high phosphate [J]. Front Physiol, 2020, 10: 1584.
[22]
Balogh E, Tóth A, Méhes G, et al. Hypoxia triggers osteochondrogenic differentiation of vascular smooth muscle cells in an HIF-1 (hypoxia-inducible factor 1)-dependent and reactive oxygen species-dependent manner [J]. Arterioscler Thromb Vasc Biol, 2019, 39(6): 1088-1099.
[23]
Knowles HJ. Distinct roles for the hypoxia-inducible transcription factors HIF-1α and HIF-2α in human osteoclast formation and function [J]. Sci Rep, 2020, 10(1): 21072.
[24]
Merceron C, Ranganathan K, Wang E, et al. Hypoxia-inducible factor 2α is a negative regulator of osteoblastogenesis and bone mass accrual [J]. Bone Res, 2019, 7: 7.
[25]
Zhou YM, Yang YY, Jing YX, et al. BMP9 reduces bone loss in ovariectomized mice by dual regulation of bone remodeling [J]. J Bone Miner Res, 2020, 35(5): 978-993.
[26]
朱冬燕,刘海岭,魏雅娟. 骨硬化蛋白在慢性肾脏病-矿物质和骨代谢异常中的研究进展[J]. 中国中西医结合肾病杂志2020, 21(9): 832-835.
[27]
Yorgan TA, Peters S, Jeschke A, et al. The anti-osteoanabolic function of sclerostin is blunted in mice carrying a high bone mass mutation of Lrp5 [J]. J Bone Miner Res, 2015, 30(7): 1175-1183.
[28]
Stegen S, Stockmans I, Moermans K, et al. Osteocytic oxygen sensing controls bone mass through epigenetic regulation of sclerostin [J]. Nat Commun, 2018, 9(1): 2557.
[29]
Miyauchi Y, Sato Y, Kobayashi T, et al. HIF1α is required for osteoclast activation by estrogen deficiency in postmenopausal osteoporosis [J]. Proc Natl Acad Sci USA, 2013, 110(41): 16568-16573.
[30]
Zhu J, Tang Y, Wu Q, et al. HIF-1α facilitates osteocyte-mediated osteoclastogenesis by activating JAK2/STAT3 pathway in vitro [J]. J Cell Physiol, 2019, 234(11): 21182-21192.
[31]
Hulley PA, Bishop T, Vernet A, et al. Hypoxia-inducible factor 1-alpha does not regulate osteoclastogenesis but enhances bone resorption activity via prolyl-4-hydroxylase 2 [J]. J Pathol, 2017, 242(3): 322-333.
[32]
Andrukhova O, Schüler C, Bergow C, et al. Augmented fibroblast growth factor-23 secretion in bone locally contributes to impaired bone mineralization in chronic kidney disease in mice [J]. Front Endocrinol (Lausanne), 2018, 9: 311.
[33]
Pereira RC, Salusky IB, Roschger P, et al. Impaired osteocyte maturation in the pathogenesis of renal osteodystrophy [J]. Kidney Int, 2018, 94(5): 1002-1012.
[34]
Yamamoto S, Koyama D, Igarashi R, et al. Serum endocrine fibroblast growth factors as potential biomarkers for chronic kidney disease and various metabolic dysfunctions in aged patients [J]. Intern Med, 2020, 59(3): 345-355.
[35]
Clinkenbeard EL, Farrow EG, Summers LJ, et al. Neonatal iron deficiency causes abnormal phosphate metabolism by elevating FGF23 in normal and ADHR mice [J]. J Bone Miner Res, 2014, 29(2): 361-389.
[36]
Ito N, Wijenayaka AR, Prideaux M, et al. Regulation of FGF23 expression in IDG-SW3 osteocytes and human bone by pro-inflammatory stimuli [J]. Mol Cell Endocrinol, 2015, 399: 208-218.
[37]
Rodelo-Haad C, Santamaria R, Muñoz-Castañeda JR, et al. FGF23, biomarker or target? [J]. Toxins (Basel), 2019, 11(3): 175.
[38]
Daryadel A, Bettoni C, Haider T, et al. Erythropoietin stimulates fibroblast growth factor 23 (FGF23) in mice and men [J]. Pflugers Arch, 2018, 470(10): 1569-1582.
[39]
Noonan ML, Ni P, Agoro R, et al. The HIF-PHI BAY 85-3934 (Molidustat) improves anemia and is associated with reduced levels of circulating FGF23 in a CKD mouse model [J]. J Bone Miner Res, 2021, 36(6): 1117-1130.
[40]
Elias RM, Dalboni MA, Coelho ACE, et al. CKD-MBD: from the pathogenesis to the identification and development of potential novel therapeutic targets [J]. Curr Osteoporos Rep, 2018, 16(6): 693-702.
[1] 蚁淳, 袁冬生, 熊学军. 系统免疫炎症指数与骨密度降低和骨质疏松的关联[J/OL]. 中华关节外科杂志(电子版), 2024, 18(05): 609-617.
[2] 王振宇, 张洪美, 荆琳, 何名江, 闫奇. 膝骨关节炎相关炎症因子与血浆代谢物间的因果关系及中介效应[J/OL]. 中华损伤与修复杂志(电子版), 2024, 19(06): 467-473.
[3] 张洁, 罗小霞, 余鸿. 系统性免疫炎症指数对急性胰腺炎患者并发器官功能损伤的预测价值[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 68-71.
[4] 唐梅, 周丽, 牛岑月, 周小童, 王倩. ICG荧光导航的腹腔镜肝切除术临床意义[J/OL]. 中华普外科手术学杂志(电子版), 2024, 18(06): 655-658.
[5] 付成旺, 杨大刚, 王榕, 李福堂. 营养与炎症指标在可切除胰腺癌中的研究进展[J/OL]. 中华普外科手术学杂志(电子版), 2024, 18(06): 704-708.
[6] 高娟, 徐建庆, 闫芳, 丁盛华, 刘霞. Rutkow、TAPP、TEP 手术治疗单侧腹股沟疝患者的临床疗效及对血清炎症因子水平的影响[J/OL]. 中华疝和腹壁外科杂志(电子版), 2024, 18(06): 675-680.
[7] 邢嘉翌, 龚佳晟, 祝佳佳, 陆群. 肺癌化疗患者继发肺部感染的病原菌耐药性及炎症因子变化分析[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(05): 714-718.
[8] 李智, 冯芸. NF-κB 与MAPK 信号通路及其潜在治疗靶点在急性呼吸窘迫综合征中的研究进展[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(05): 840-843.
[9] 孙璐, 蒋亚玲, 陈凌君. 布托啡诺对脑缺血再灌注损伤大鼠神经炎症和JAK2/STAT3信号通路的影响[J/OL]. 中华细胞与干细胞杂志(电子版), 2024, 14(06): 344-350.
[10] 张龙, 孙善柯, 徐伟, 李文柱, 李俊达, 池涌泉, 何广胜, 成峰, 王学浩, 饶建华. 腹腔镜脾切除治疗血液系统疾病的临床疗效分析[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 870-875.
[11] 程柏凯, 杨光. 高胰岛素-正葡萄糖钳夹技术评估慢性肾脏病患者胰岛素抵抗的研究进展[J/OL]. 中华肾病研究电子杂志, 2024, 13(06): 334-339.
[12] 王贝贝, 崔振义, 王静, 王晗妍, 吕红芝, 李秀婷. 老年股骨粗隆间骨折患者术后贫血预测模型的构建与验证[J/OL]. 中华老年骨科与康复电子杂志, 2024, 10(06): 355-362.
[13] 杭丽, 张耀辉, 孙文恺. 参菝抗瘤液对结直肠腺瘤性息肉术后肠道功能、炎症指标及复发情况的影响[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(05): 413-416.
[14] 王湛, 李文坤, 杨奕, 徐芳, 周敏思, 苏珈仪, 王亚丹, 吴静. 炎症指标在早发性结直肠肿瘤中的应用[J/OL]. 中华临床医师杂志(电子版), 2024, 18(09): 802-810.
[15] 奚培培, 周加军. 慢性肾脏病患者肌少症机制和诊治的研究进展[J/OL]. 中华临床医师杂志(电子版), 2024, 18(05): 491-495.
阅读次数
全文


摘要