切换至 "中华医学电子期刊资源库"

中华肾病研究电子杂志 ›› 2022, Vol. 11 ›› Issue (03) : 167 -171. doi: 10.3877/cma.j.issn.2095-3216.2022.03.010

综述

细胞外囊泡在急性肾损伤中的作用研究进展
陆梦婷1, 包嘉欣1, 曹长春1,()   
  1. 1. 211100 南京医科大学附属逸夫医院肾内科
  • 收稿日期:2022-02-07 出版日期:2022-06-28
  • 通信作者: 曹长春
  • 基金资助:
    国家自然科学基金(82170698)

Research progress on the role of extracellular vesicles in acute kidney injury

Mengting Lu1, Jiaxin Bao1, Changchun Cao1,()   

  1. 1. Department of Nephrology, Sir Run Run Hospital, Nanjing Medical University, Nanjing 211100, Jiangsu Province, China
  • Received:2022-02-07 Published:2022-06-28
  • Corresponding author: Changchun Cao
引用本文:

陆梦婷, 包嘉欣, 曹长春. 细胞外囊泡在急性肾损伤中的作用研究进展[J/OL]. 中华肾病研究电子杂志, 2022, 11(03): 167-171.

Mengting Lu, Jiaxin Bao, Changchun Cao. Research progress on the role of extracellular vesicles in acute kidney injury[J/OL]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2022, 11(03): 167-171.

急性肾损伤(AKI)是一组多种原因引起的以肾功能快速下降及代谢废物蓄积为表现的危重综合征。AKI的发病率日渐增高,且在重症监护病房中有很高的死亡率。目前,临床上依据血肌酐及尿量诊断AKI,并不能敏感和及时地提示肾损伤,并且对于AKI的治疗尚无有效手段。尿液中的细胞外囊泡(EVs)来源于肾脏固有细胞,参与肾脏的病理生理过程,在AKI过程中起重要作用。此外,EVs作为天然的纳米级膜囊泡,可靶向肾脏输送治疗性分子,减轻肾损伤。本文综述了EVs的种类、识别、生理功能,并着重介绍EVs在AKI中的诊断和治疗价值。

Acute kidney injury (AKI) is a group of critical syndromes, which is caused by multiple causes and characterized by rapid decline in renal function and accumulation of metabolic waste. The incidence of AKI is increasing, and it has a high mortality rate in the intensive care unit. Currently, the clinical diagnosis of AKI is based on the level of serum creatinine and the urine output, which are not sensitive and timely to indicate renal injury. And there are no effective methods for the treatment of AKI yet. Extracellular vesicles (EVs) in the urine are derived from the renal intrinsic cells, and participate in the pathophysiological process of the kidney, playing an important role in the process of AKI. In addition, EVs are natural nano-scale membrane vesicles that can be used for targeting the kidney to deliver therapeutic molecules and alleviate the kidney damage. This article reviewed the types, recognition, and physiological functions of EVs, and focused on the diagnostic and therapeutic value of EVs in AKI.

表1 细胞外囊泡作为急性肾损伤的诊断标志物
表2 细胞外囊泡在急性肾损伤的治疗作用
[1]
Ronco C, Bellomo R, Kellum JA. Acute kidney injury [J]. Lancet, 2019, 394(10212): 1949-1964.
[2]
Hoste EAJ, Kellum JA, Selby NM, et al. Global epidemiology and outcomes of acute kidney injury [J]. Nat Rev Nephrol, 2018, 14(10): 607-625.
[3]
James MT, Bhatt M, Pannu N, et al. Long-term outcomes of acute kidney injury and strategies for improved care [J]. Nat Rev Nephrol, 2020, 16(4): 193-205.
[4]
Shah R, Patel T, Freedman JE. Circulating extracellular vesicles in human disease [J]. N Engl J Med, 2018, 379(10): 958-966.
[5]
Blander JM. The many ways tissue phagocytes respond to dying cells [J]. Immunol Rev, 2017, 277(1): 158-173.
[6]
Ma L, Li Y, Peng J, et al. Discovery of the migrasome, an organelle mediating release of cytoplasmic contents during cell migration [J]. Cell Res, 2015, 25(1): 24-38.
[7]
Théry C, Witwer KW, Aikawa E, et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines [J]. J Extracell Vesicles, 2018, 7(1): 1535750.
[8]
Crowley LC, Marfell BJ, Scott AP, et al. Quantitation of apoptosis and necrosis by annexin V binding, propidium iodide uptake, and flow cytometry [J]. Cold Spring Harb Protoc, 2016, 2016(11): doi: 10.1101/pdb.prot087288.
[9]
Zhao X, Lei Y, Zheng J, et al. Identification of markers for migrasome detection [J]. Cell Discov, 2019, 5: 27.
[10]
Görgens A, Bremer M, Ferrer-Tur R, et al. Optimisation of imaging flow cytometry for the analysis of single extracellular vesicles by using fluorescence-tagged vesicles as biological reference material [J]. J Extracell Vesicles, 2019, 8(1): 1587567.
[11]
Pienimaeki-Roemer A, Kuhlmann K, Böttcher A, et al. Lipidomic and proteomic characterization of platelet extracellular vesicle subfractions from senescent platelets [J]. Transfusion, 2015, 55(3): 507-521.
[12]
Turchinovich A, Drapkina O, Tonevitsky A. Transcriptome of extracellular vesicles: state-of-the-art [J]. Front Immunol, 2019, 10: 202.
[13]
Battistelli M, Falcieri E. Apoptotic bodies: particular extracellular vesicles involved in intercellular communication [J]. Biology (Basel), 2020, 9(1): 21.
[14]
Zhou H, Pisitkun T, Aponte A, et al. Exosomal fetuin-A identified by proteomics: a novel urinary biomarker for detecting acute kidney injury [J]. Kidney Int, 2006, 70(10): 1847-1857.
[15]
Panich T, Chancharoenthana W, Somparn P, et al. Urinary exosomal activating transcriptional factor 3 as the early diagnostic biomarker for sepsis-induced acute kidney injury [J]. BMC Nephrol, 2017, 18(1): 10.
[16]
Chen HH, Lai PF, Lan YF, et al. Exosomal ATF3 RNA attenuates pro-inflammatory gene MCP-1 transcription in renal ischemia-reperfusion [J]. J Cell Physiol, 2014, 229(9): 1202-1211.
[17]
Bulacio RP, Anzai N, Ouchi M, et al. Organic anion transporter 5 (Oat5) urinary excretion is a specific biomarker of kidney injury: evaluation of urinary excretion of exosomal Oat5 after N-acetylcysteine prevention of cisplatin induced nephrotoxicity [J]. Chem Res Toxicol, 2015, 28(8): 1595-1602.
[18]
du Cheyron D, Daubin C, Poggioli J, et al. Urinary measurement of Na+/H+ exchanger isoform 3 (NHE3) protein as new marker of tubule injury in critically ill patients with ARF [J]. Am J Kidney Dis, 2003, 42(3): 497-506.
[19]
Asvapromtada S, Sonoda H, Kinouchi M, et al. Characterization of urinary exosomal release of aquaporin-1 and -2 after renal ischemia-reperfusion in rats [J]. Am J Physiol Renal Physiol, 2018, 314(4): F584-F601.
[20]
Saito M, Horie S, Yasuhara H, et al. Metabolomic profiling of urine-derived extracellular vesicles from rat model of drug-induced acute kidney injury [J]. Biochem Biophys Res Commun, 2021, 546: 103-110.
[21]
Sonoda H, Lee BR, Park KH, et al. miRNA profiling of urinary exosomes to assess the progression of acute kidney injury [J]. Sci Rep, 2019, 9(1): 4692.
[22]
Lv LL, Feng Y, Wu M, et al. Exosomal miRNA-19b-3p of tubular epithelial cells promotes M1 macrophage activation in kidney injury [J]. Cell Death Differ, 2020, 27(1): 210-226.
[23]
Yun CY, Lim JH, Oh JH, et al. Urinary exosomal microRNA-21 as a marker for scrub typhus-associated acute kidney injury [J]. Genet Test Mol Biomarkers, 2021, 25(2): 140-144.
[24]
Lee HK, Lee BR, Lee TJ, et al. Differential release of extracellular vesicle tRNA from oxidative stressed renal cells and ischemic kidneys [J]. Sci Rep, 2022, 12(1): 1646.
[25]
Tökés-Füzesi M, Woth G, Ernyey B, et al. Microparticles and acute renal dysfunction in septic patients [J]. J Crit Care, 2013, 28(2): 141-147.
[26]
Wu XQ, Tian XY, Wang ZW, et al. miR-191 secreted by platelet-derived microvesicles induced apoptosis of renal tubular epithelial cells and participated in renal ischemia-reperfusion injury via inhibiting CBS [J]. Cell Cycle, 2019, 18(2): 119-129.
[27]
Zhao M, Liu S, Wang C, et al. Mesenchymal stem cell-derived extracellular vesicles attenuate mitochondrial damage and inflammation by stabilizing mitochondrial DNA [J]. ACS Nano, 2021, 15(1): 1519-1538.
[28]
Cao JY, Wang B, Tang TT, et al. Exosomal miR-125b-5p deriving from mesenchymal stem cells promotes tubular repair by suppression of p53 in ischemic acute kidney injury [J]. Theranostics, 2021, 11(11): 5248-5266.
[29]
Zhu G, Pei L, Lin F, et al. Exosomes from human-bone-marrow-derived mesenchymal stem cells protect against renal ischemia/reperfusion injury via transferring miR-199a-3p [J]. J Cell Physiol, 2019, 234(12): 23736-23749.
[30]
Collino F, Bruno S, Incarnato D, et al. AKI recovery induced by mesenchymal stromal cell-derived extracellular vesicles carrying microRNAs [J]. J Am Soc Nephrol, 2015, 26(10): 2349-2360.
[31]
Ullah M, Liu DD, Rai S, et al. HSP70-mediated NLRP3 inflammasome suppression underlies reversal of acute kidney injury following extracellular vesicle and focused ultrasound combination therapy [J]. Int J Mol Sci, 2020, 21(11): 4085.
[32]
Ullah M, Liu DD, Rai S, et al. Pulsed focused ultrasound enhances the therapeutic effect of mesenchymal stromal cell-derived extracellular vesicles in acute kidney injury [J]. Stem Cell Res Ther, 2020, 11(1): 398.
[33]
Cao J, Wang B, Tang T, et al. Three-dimensional culture of MSCs produces exosomes with improved yield and enhanced therapeutic efficacy for cisplatin-induced acute kidney injury [J]. Stem Cell Res Ther, 2020, 11(1): 206.
[34]
Ullah M, Liu DD, Rai S, et al. A novel approach to deliver therapeutic extracellular vesicles directly into the mouse kidney via its arterial blood supply [J]. Cells, 2020, 9(4): 937.
[35]
Gao F, Zuo B, Wang Y, et al. Protective function of exosomes from adipose tissue-derived mesenchymal stem cells in acute kidney injury through SIRT1 pathway [J]. Life Sci, 2020, 255: 117719.
[36]
Li Y, Meng Y, Zhu X, et al. Metabolic syndrome increases senescence-associated micro-RNAs in extracellular vesicles derived from swine and human mesenchymal stem/stromal cells [J]. Cell Commun Signal, 2020, 18(1): 124.
[37]
Collino F, Lopes JA, Corrêa S, et al. Adipose-derived mesenchymal stromal cells under hypoxia: changes in extracellular vesicles secretion and improvement of renal recovery after ischemic injury [J]. Cell Physiol Biochem, 2019, 52(6): 1463-1483.
[38]
Zhang K, Chen S, Sun H, et al. In vivo two-photon microscopy reveals the contribution of Sox9+ cell to kidney regeneration in a mouse model with extracellular vesicle treatment [J]. J Biol Chem, 2020, 295(34): 12203-12213.
[39]
Collino F, Lopes JA, Tapparo M, et al. Extracellular vesicles derived from induced pluripotent stem cells promote renoprotection in acute kidney injury model [J]. Cells, 2020, 9(2): 453.
[40]
Li X, Liao J, Su X, et al. Human urine-derived stem cells protect against renal ischemia/reperfusion injury in a rat model via exosomal miR-146a-5p which targets IRAK1 [J]. Theranostics, 2020, 10(21): 9561-9578.
[41]
Tang TT, Wang B, Wu M, et al. Extracellular vesicle-encapsulated IL-10 as novel nanotherapeutics against ischemic AKI [J]. Sci Adv, 2020, 6(33): eaaz0748.
[42]
Kim S, Lee SA, Yoon H, et al. Exosome-based delivery of super-repressor IκBα ameliorates kidney ischemia-reperfusion injury [J]. Kidney Int, 2021, 100(3): 570-584.
[43]
Tang TT, Wang B, Li ZL, et al. Kim-1 targeted extracellular vesicles: a new therapeutic platform for RNAi to treat AKI [J]. J Am Soc Nephrol, 2021, 32(10): 2467-2483.
[1] 王亚红, 蔡胜, 葛志通, 杨筱, 李建初. 颅骨骨膜窦的超声表现一例[J/OL]. 中华医学超声杂志(电子版), 2024, 21(11): 1089-1091.
[2] 史学兵, 谢迎东, 谢霓, 徐超丽, 杨斌, 孙帼. 声辐射力弹性成像对不可切除肝细胞癌门静脉癌栓患者放射治疗效果的评价[J/OL]. 中华医学超声杂志(电子版), 2024, 21(08): 778-784.
[3] 严华悦, 刘子祥, 周少波. 磷酸烯醇式丙酮酸羧激酶-1在恶性肿瘤中的研究进展[J/OL]. 中华普通外科学文献(电子版), 2024, 18(06): 452-456.
[4] 高俊颖, 张海洲, 区泓乐, 孙强. FOLFOX-HAIC 为基础的肝细胞癌辅助转化治疗的应用进展[J/OL]. 中华普通外科学文献(电子版), 2024, 18(06): 457-463.
[5] 李华志, 曹广, 刘殿刚, 张雅静. 不同入路下行肝切除术治疗原发性肝细胞癌的临床对比[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 52-55.
[6] 陈浩, 王萌. 胃印戒细胞癌的临床病理特征及治疗选择的研究进展[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 108-111.
[7] 刘柏隆, 周祥福. 压力性尿失禁阶梯治疗的项目介绍[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2025, 19(01): 125-125.
[8] 刘柏隆. 女性压力性尿失禁阶梯治疗之手术治疗方案选择[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2025, 19(01): 126-126.
[9] 李浩, 陈棋帅, 费发珠, 张宁伟, 李元东, 王硕晨, 任宾. 慢性肝病肝纤维化无创诊断的研究进展[J/OL]. 中华临床医师杂志(电子版), 2024, 18(09): 863-867.
[10] 谭瑞义. 小细胞骨肉瘤诊断及治疗研究现状与进展[J/OL]. 中华临床医师杂志(电子版), 2024, 18(08): 781-784.
[11] 王誉英, 刘世伟, 王睿, 曾娅玲, 涂禧慧, 张蒲蓉. 老年乳腺癌新辅助治疗病理完全缓解的预测因素分析[J/OL]. 中华临床医师杂志(电子版), 2024, 18(07): 641-646.
[12] 王子阳, 王宏宾, 刘晓旌. 血清标志物对甲胎蛋白阴性肝细胞癌诊断的研究进展[J/OL]. 中华临床医师杂志(电子版), 2024, 18(07): 677-681.
[13] 陈慧, 邹祖鹏, 周田田, 张艺丹, 张海萍. 皮肤镜对头皮红斑性皮肤病辅助鉴别诊断的研究进展[J/OL]. 中华临床医师杂志(电子版), 2024, 18(07): 692-698.
[14] 颜世锐, 熊辉. 感染性心内膜炎合并急性肾损伤患者的危险因素探索及死亡风险预测[J/OL]. 中华临床医师杂志(电子版), 2024, 18(07): 618-624.
[15] 崔军威, 蔡华丽, 胡艺冰, 胡慧. 亚甲蓝联合金属定位夹及定位钩针标记在乳腺癌辅助化疗后评估腋窝转移淋巴结的临床应用价值探究[J/OL]. 中华临床医师杂志(电子版), 2024, 18(07): 625-632.
阅读次数
全文


摘要