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中华肾病研究电子杂志 ›› 2023, Vol. 12 ›› Issue (02) : 101 -104. doi: 10.3877/cma.j.issn.2095-3216.2023.02.008

综述

罗沙司他在炎症反应中的作用研究进展
王星月1, 舒亮辉1, 朝亚1,()   
  1. 1. 214044 苏州大学附属无锡市第九人民医院肾内科
  • 收稿日期:2021-08-23 出版日期:2023-04-28
  • 通信作者: 朝亚
  • 基金资助:
    无锡市卫健委青年科研项目(Q201753)

Progress of research on the role of roxadustat in inflammatory reaction

Xingyue Wang1, Lianghui Shu1, Ya Chao1,()   

  1. 1. Department of Nephrology, Wuxi Ninth People′s Hospital Affiliated to Suzhou University, Wuxi 214044, Jiangsu Province, China
  • Received:2021-08-23 Published:2023-04-28
  • Corresponding author: Ya Chao
引用本文:

王星月, 舒亮辉, 朝亚. 罗沙司他在炎症反应中的作用研究进展[J/OL]. 中华肾病研究电子杂志, 2023, 12(02): 101-104.

Xingyue Wang, Lianghui Shu, Ya Chao. Progress of research on the role of roxadustat in inflammatory reaction[J/OL]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2023, 12(02): 101-104.

罗沙司他是一种口服的缺氧诱导因子(HIF)脯氨酰羟化酶的抑制剂,可刺激红细胞生成并改善铁代谢,目前主要用于治疗肾性贫血。已有研究发现,罗沙司他通过稳定HIF表达,还可以调节人体的免疫反应和急、慢性炎症反应。本文综述了近年来有关罗沙司他在炎症反应中的作用与机制研究进展,为其临床应用提供参考。

Roxadustat is an oral inhibitor for the hypoxia-inducible factor (HIF) proline hydroxylase, and can stimulate erythropoiesis and improve iron metabolism, and has currently been mainly used to treat renal anemia. Studies have found that roxadustat can also regulate the immune response as well as acute and chronic inflammatory reaction by stabilizing the expression of HIF. This article reviewed the progress of research on the role and mechanism of roxadustat in inflammatory reaction in recent years in order to provide reference for its clinical application.

图1 罗沙司他通过调节缺氧诱导因子-1α稳定性介导炎症反应注:HIF-1α:缺氧诱导因子-1α;PHD:脯氨酸羟化酶;Nrf2:核因子E2相关因子2; NF-κB:核因子κB; ROS:活性氧;正常状态下PHD羟基化HIF-1α并促使其降解,而在缺氧或罗沙司他作用下HIF-1α可影响Nrf2信号通路、NF-κB通路、ROS及免疫细胞等进一步调节炎症反应
[25]
Henry D, Glaspy J, Harrup R, et al. Roxadustat for the treatment of anemia in patients with lower-risk myelodysplastic syndrome: open-label, dose-selection, lead-in stage of a phase 3 study [J]. Am J Hematol, 2022, 97(2): 174-184.
[26]
Akizawa T, Iwasaki M, Yamaguchi Y, et al. Phase 3, randomized, double-blind, active-comparator (darbepoetin alfa) study of oral roxadustat in CKD Patients with anemia on hemodialysis in Japan [J]. J Am Soc Nephrol, 2020, 31(7): 1628-1639.
[27]
Fishbane S, El-Shahawy M, Pecoits-Filho R, et al. Roxadustat for treating anemia in patients with CKD not on dialysis: results from a randomized phase 3 study [J]. J Am Soc Nephrol, 2021, 32(3): 737-755.
[28]
Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor [J]. Cell, 2020, 18(2): 271-280.
[29]
Wing P, Keeley T, Zhuang X, et al. Hypoxic and pharmacological activation of HIF inhibits SARS-CoV-2 infection of lung epithelial cells [J]. Cell Rep, 2021, 35(3):109020.
[30]
Chen N, Hao C, Peng X, et al. Roxadustat for anemia in patients with kidney disease not receiving dialysis [J]. N Engl J Med, 2019, 381(11): 1001-1010.
[31]
Provenzano R, Szczech L, Leong R, et al. Efficacy and cardiovascular safety of roxadustat for treatment of anemia in patients with non-dialysis-dependent CKD: pooled results of three randomized clinical trials [J]. Clin J Am Soc Nephrol, 2021, 16(8): 1190-1200.
[32]
Li ZL, Lv LL, Wang B, et al. The profibrotic effects of MK-8617 on tubulointerstitial fibrosis mediated by the KLF5 regulating pathway [J]. FASEB J, 2019, 33(11): 12630-12643.
[33]
Tokuyama A, Kadoya H, Obata A, et al. Roxadustat and thyroid-stimulating hormone suppression [J]. Clin Kidney J, 2021, 14(5): 1472-1474.
[34]
Luo W, Lin B, Wang Y, et al. PHD3-mediated prolyl hydroxylation of nonmuscle actin impairs polymerization and cell motility [J]. Mol Biol Cell, 2014, 25(18): 2788-2796.
[35]
Conza G, Cafarello S, Zheng X, et al. PHD2 targeting overcomes breast cancer cell death upon glucose starvation in a PP2A/B55α-mediated manner [J]. Cell Rep, 2017, 18(12): 2836-2844.
[36]
Li Z, Lv L, Tang T, et al. HIF-1α inducing exosomal microRNA-23a expression mediates the cross-talk between tubular epithelial cells and macrophages in tubulointerstitial inflammation [J]. Kidney Int, 2019, 95(2): 388-404.
[1]
Vanderhaeghen T, Vandewalle J, Libert C. Hypoxia-inducible factors in metabolic reprogramming during sepsis [J]. FEBS J, 2020, 287(8): 1478-1495.
[2]
Scholz C, Cavadas M, Tambuwala M, et al. Regulation of IL-1beta-induced NF-kappaB by hydroxylases links key hypoxic and inflammatory signaling pathways [J]. Proc Natl Acad Sci USA, 2013, 110(46): 18490-18495.
[3]
Taylor C, Doherty G, Fallon P, et al. Hypoxia-dependent regulation of inflammatory pathways in immune cells [J]. J Clin Invest, 2016, 126(10): 3716-3724.
[4]
Kobayashi H, Gilbert V, Liu Q, et al. Myeloid cell-derived hypoxia-inducible factor attenuates inflammation in unilateral ureteral obstruction-induced kidney injury [J]. J Immunol, 2012, 188(10): 5106-5115.
[5]
Yeh T, Leissing T, Abboud M, et al. Molecular and cellular mechanisms of HIF prolyl hydroxylase inhibitors in clinical trials [J]. Chem Sci, 2017, 8(11): 7651-7668.
[6]
Soilleux E, Turley H, Tian YM, et al. Use of novel monoclonal antibodies to determine the expression and distribution of the hypoxia regulatory factors PHD-1, PHD-2, PHD-3 and FIH in normal and neoplastic human tissues [J]. Histopathology, 2005, 47(6): 602-610.
[7]
Chan M, Atasoylu O, Hodson E, et al. Potent and selective triazole-based inhibitors of the hypoxia-inducible factor prolyl-hydroxylases with activity in the murine brain [J]. PLoS One, 2015, 10(7): e0132004.
[8]
Price C, Gill S, Ho ZV, et al. Genome-wide interrogation of human cancers identifies EGLN1 dependency in clear cell ovarian cancers [J]. Cancer Res, 2019, 79(10): 2564-2579.
[9]
Xie R, Fang X, Zheng X, et al. Salidroside and FG-4592 ameliorate high glucose-induced glomerular endothelial cells injury via HIF upregulation [J]. Biomed Pharmacother, 2019, 118: 109175.
[10]
Miao AF, Liang JX, Yao L, et al. Hypoxia-inducible factor prolyl hydroxylase inhibitor roxadustat (FG-4592) protects against renal ischemia/reperfusion injury by inhibiting inflammation [J]. Ren Fail, 2021, 43(1): 803-810.
[11]
Han F, Wu G, Han S, et al. Hypoxia-inducible factor prolyl-hydroxylase inhibitor roxadustat (FG-4592) alleviates sepsis-induced acute lung injury [J]. Respir Physiol Neurobiol, 2020, 281: 103506.
[12]
Yang DG, Gao YY, Yin ZQ, et al. Roxadustat alleviates nitroglycerin-induced migraine in mice by regulating HIF-1α/NF-κB/inflammation pathway [J]. Acta Pharmacol Sin, 2023, 44(2): 308-320.
[13]
Eleftheriadis1 T, Pissas1 G, Mavropoulos A, et al. In mixed lymphocyte reaction, the hypoxia-inducible factor prolyl-hydroxylase inhibitor roxadustat suppresses cellular and humoral alloimmunity [J]. Arch Immunol Ther Exp, 2020, 68(6): 31.
[14]
Yang Y, Yu X, Zhang Y, et al. Hypoxia-inducible factor prolyl hydroxylase inhibitor roxadustat (FG-4592) protects against cisplatin-induced acute kidney injury [J]. Clin Sci (Lond), 2018, 132(7): 825-838.
[15]
Li X, Zou Y, Xing J, et al. Pretreatment with roxadustat (FG-4592) attenuates folic acid-induced kidney injury through antiferroptosis via Akt/GSK-3beta/Nrf2 pathway [J]. Oxid Med Cell Longev, 2020, 2020: 6286984.
[16]
Schley G, Klanke B, Kalucka J, et al. Mononuclear phagocytes orchestrate prolyl hydroxylase inhibition-mediated renoprotection in chronic tubulointerstitial nephritis [J]. Kidney Int, 2019, 96(2): 378-396.
[17]
Gao Y, Jiang X, Yang D, et al. Roxadustat, a hypoxia-inducible factor 1α activator, attenuates both long- and short-term alcohol-induced alcoholic liver disease [J]. Front Pharmacol, 2022, 13: 895710.
[18]
Yoshida T, Okumura T, Matsuo Y, et al. Activation of transcription factor HIF inhibits IL-1β-induced NO production in primary cultured rat hepatocytes [J]. Nitric Oxide, 2022, 124: 1-14.
[19]
Chen N, Hao C, Liu B, et al. Roxadustat treatment for anemia in patients undergoing long-term dialysis [J]. N Engl J Med, 2019, 381(11): 1011-1022.
[20]
Besarab A, Chernyavskaya E, Motylev I, et al. Roxadustat (FG-4592): correction of anemia in incident dialysis patients [J]. J Am Soc Nephrol, 2016, 27(4): 1225-1233.
[21]
Provenzano R, Besarab A, Sun C, et al. Oral hypoxia-inducible factor prolyl hydroxylase inhibitor roxadustat (FG-4592) for the treatment of anemia in patients with CKD [J]. Clin J Am Soc Nephrol, 2016, 11(6): 982-991.
[22]
Provenzano R, Besarab A, Wright S, et al. Roxadustat (FG-4592) versus epoetin alfa for anemia in patients receiving maintenance hemodialysis: a phase 2, randomized, 6- to 19-week, open-label, active-comparator, dose-ranging, safety and exploratory efficacy study [J]. Am J Kidney Dis, 2016, 67(6): 912-924.
[23]
陈豫闽,刘俊英,贾国强,等. 罗沙司他在维持性腹膜透析患者肾性贫血治疗中的应用效果[J]. 广东医学2021, 2(5): 216-220.
[24]
孙艳玲,谢华,康喆,等. 罗沙司他治疗初始血液透析患者肾性贫血20例疗效研究 [J]. 中国实用内科杂志2020, 11(5): 942-946.
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