外泌体中相关肾脏疾病研究进展
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摘要
外泌体是一种包含大量生物信息的膜性囊泡,研究发现其能反映来源细胞的生理和病理状态,并作为细胞间信号分子发挥重要作用。基于其生物学特点,近年肾脏疾病及肾损伤机制的研究和治疗日趋深入。主要针对:(1)寻求判断肾脏损害程度的无创生物标记物。(2)对各类型肾病损害机制研究。(3)研究其在特异性治疗上的可行性分析。该文通过对已有相关文献的综述,可预见外泌体作为肾脏疾病的新兴诊疗手段,在未来对肾脏疾病各层面研究会成为新的突破方向。
Exosomes are membranous vesicles containing a large amount of biological information. They have been found to reflect the physiological and pathological conditions of the source cells and play an important role as intercellular signaling molecules. Based on its biological characteristics,the research and treatment of kidney diseases and renal injury mechanisms have become increasingly sophisticated in recent years,focusing on:(1)Exploring non-invasive biomarkers of renal damage.(2)Studying the mechanism of various types of nephropathy.(3)To investigate the feasibility of specific treatment. In this paper,through the review of related literature,it is expected that exosome as a new diagnosis and treatment method for kidney disease will become a new breakthrough direction in the future research on various aspects of kidney disease.
Exosomes are membranous vesicles containing a large amount of biological information. They have been found to reflect the physiological and pathological conditions of the source cells and play an important role as intercellular signaling molecules. Based on its biological characteristics,the research and treatment of kidney diseases and renal injury mechanisms have become increasingly sophisticated in recent years,focusing on:(1)Exploring non-invasive biomarkers of renal damage.(2)Studying the mechanism of various types of nephropathy.(3)To investigate the feasibility of specific treatment. In this paper,through the review of related literature,it is expected that exosome as a new diagnosis and treatment method for kidney disease will become a new breakthrough direction in the future research on various aspects of kidney disease.
引文
[1]Sato K,Meng F,Glaser S,et al. Exosomes in liver pathology[J].Journal of Hepatology,2016,65(1):213-221.
[2]Kim DK,Kang B,Kim OY,et al. EVpedia:an integrated database of high-throughput data for systemic analyses of extracellular vesicles[J]. Journal of Extracellular Vesicles,2013,2(1):20384.
[3]Yu X,Odenthal M,Fries JWU. Exosomes as miRNA carriers:formation-function-future[J]. International Journal of Molecular Sciences,2016,17(12):2028.
[4]ooijmans SAA,Schiffelers RM,Zarovni N,et al. Modulation of tissue tropism and biological activity of exosomes and other extracellular vesicles:New nanotools for cancer treatment[J].Pharmacological Research,2016,111:487-500.
[5]Huotari J,Helenius A. Endosome maturation[J]. The EMBO Journal,2011,30(17):3481-3500.
[6]Gildea JJ,Seaton JE,Victor KG,et al. Exosomal transfer from human renal proximal tubule cells to distal tubule and collecting duct cells[J]. Clinical Biochemistry,2014,47:89-94,2014.
[7]朱迎星,郑萍,赵绍林,等.尿exosomes的分离方法及在临床中应用研究进展[J].中华临床医师杂志(电子版),2016(14):32.
[8]Sharma S,Scholz-Romero K,Rice GE,et al. Methods to Enrich Exosomes from Conditioned Media and Biological Fluids[M].New York:Humana Press,2018:103-115.
[9]Li P,Kaslan M,Lee S H,et al. Progress in exosome isolation techniques[J]. Theranostics,2017,7(3):789.
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[12]Eissa S,Matboli M,Aboushahba R,et al. Urinary exosomal microRNA panel unravels novel biomarkers for diagnosis of type 2 diabetic kidney disease[J]. Journal of Diabetes and its Complications,2016,30(8):1585-1592.
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[14]Zubiri I,Posada-Ayala M,Sanz-Maroto A,et al. Diabetic nephropathy induces changes in the proteome of human urinary exosomes as revealed by label-free comparative analysis[J]. J Proteomics,2014,96:92-102.
[15]Kalani A,Mohan A,Godbole MM,et al. Wilm's tumor-1 protein levels in urinary exosomes from diabetic patients with or without proteinuria[J]. PLoS One,2013,8(3):e60177.
[16]Xiaoming WU,Yanbin GAO. Exosomes from high glucosetreated glomerular endothelial cells activate mesangial cells to promote renal fibrosis[J].Biol Open,2016,5(4):484-491.
[17]WANG YY,TANG LQ,WEI W. Berberine attenuates podocytes injury caused by exosomes derived from high glucose-induced mesangial cells through TGFβ1-PI3K/AKT pathway[J].European Journal of Pharmacology,2018,1:34.
[18]SUN H,YAO W,TANG Y,et al. Urinary exosomes as a novel biomarker for evaluation ofα-lipoic acid's protective effect in early diabetic nephropathy[J]. Journal of Clinical Laboratory Analysis,2017,31(6):22129.
[19]WU S,WANG Z,Bharadwaj S,et al. Implantation of autologous urine derived stem cells expressing vascular endothelial growth factor for potential use in genitourinary reconstruction[J]. The Journal of Urology,2011,186(2):640-647.
[20]ZHANG Y,McNeill E,TIAN H,et al. Urine derived cells are a potential source for urological tissue reconstruction[J]. The Journal of Urology,2008,180(5):2226-2233.
[21]Timmers L,Lim S K,Arslan F,et al. Reduction of myocardial infarct size by human mesenchymal stem cell conditioned medium[J]. Stem Cell Research,2008,1(2):129-137.
[22]JIANG Z,LIU Y,NIU X,et al. Exosomes secreted by human urine-derived stem cells could prevent kidney complications from type I diabetes in rats[J]. Stem Cell Research&Therapy,2016,7(1):24.
[23]PIMPI Khurana R,Ranches G,Schafferer S,et al. Identification of urinary exosomal noncoding RNAs as novel biomarkers in chronic kidney disease[J]. RNA,2017,23(2):142-152.
[24]Lange T,Stracke S,Rettig R,et al. Identification of miR-16 as an endogenous reference gene for the normalization of urinary exosomal miRNA expression data from CKD patients[J].PloS One,2017,12(8):e0183435.
[25]Moon P G,Lee J E,You S,et al. Proteomic analysis of urinary exosomes from patients of early IgA nephropathy and thin basement membrane nephropathy[J]. Proteomics,2011,11(12):2459-2475.
[26]MIN QH,CHEN XM,ZOU YQ,et al. Differential expression of urinary exosomal micro RNA s in IgA nephropathy[J]. Journal of Clinical Laboratory Analysis,2018,32(2):e22226.
[27]FENG Y,LYU L,WU W,et al. Mp351 urinary exosomes and the loading of Ccl2 mrna as biomarker of iga nephropathy patients[J]. Nephrology Dialysis Transplantation,2017,32(suppl_3):555-556.
[28]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]. American Journal of Kidney Diseases,2003,42(3):497-506.
[29]Caglar K,Yilmaz M I,Saglam M,et al. Endothelial dysfunction and fetuin a levels before and after kidney transplantation[J].Transplantation,2007,83(4):392-397.
[30]ZHOU H,Cheruvanky A,HU X,et al. Urinary exosomal transcription factors,a new class of biomarkers for renal disease[J]. Kidney International,2008,74(5):613-621.
[31]Sonoda H,Yokota-Ikeda N,Oshikawa S,et al. Decreased abundance of urinary exosomal aquaporin-1 in renal ischemiareperfusion injury[J]. American Journal of Physiology-Renal Physiology,2009,297(4):F1006-F1016.
[32]YU Y,BAI F,QIN N,et al. Non-proximal renal tubule-derived urinary exosomal miR-200b as a biomarker of renal fibrosis[J].Nephron,2018,10:1159.
[33]HUANG Z,ZHANG Y,ZHOU J,et al. Urinary exosomal miR-193a can be a potential biomarker for the diagnosis of primary focal segmental glomerulosclerosis in children[J]. Bio Med Research International,2017,2017:1115.
[34]Henriett Butzab,Roy Nofech-Mozesa,Qiang Dinga,et al.Exosomal microRNAs are diagnostic biomarkers and can mediate cell-cell communication in renal cell carcinoma[J]. European Urology Focus,2016,2(2):210-218.
[35]De Palma G,Sallustio F,Curci C,et al. The three-gene signature in urinary extracellular vesicles from patients with clear cell renal cell carcinoma[J]. Journal of Cancer,2016,7(14):1960.
[36]Torres V E,Harris P C,Pirson Y. Autosomal dominant polycystic kidney disease[J]. The Lancet,2007,369(9569):1287-1301.
[37]Hogan M C,Manganelli L,Woollard J R,et al. Characterization of PKD protein-positive exosome-like vesicles[J]. Journal of the American Society of Nephrology,2009,20(2):278-288.
[38]Hogan M C,Bakeberg J L,Gainullin V G,et al. Identification of biomarkers for PKD1 using urinary exosomes[J]. Journal of the American Society of Nephrology,2014,16:40354.
[2]Kim DK,Kang B,Kim OY,et al. EVpedia:an integrated database of high-throughput data for systemic analyses of extracellular vesicles[J]. Journal of Extracellular Vesicles,2013,2(1):20384.
[3]Yu X,Odenthal M,Fries JWU. Exosomes as miRNA carriers:formation-function-future[J]. International Journal of Molecular Sciences,2016,17(12):2028.
[4]ooijmans SAA,Schiffelers RM,Zarovni N,et al. Modulation of tissue tropism and biological activity of exosomes and other extracellular vesicles:New nanotools for cancer treatment[J].Pharmacological Research,2016,111:487-500.
[5]Huotari J,Helenius A. Endosome maturation[J]. The EMBO Journal,2011,30(17):3481-3500.
[6]Gildea JJ,Seaton JE,Victor KG,et al. Exosomal transfer from human renal proximal tubule cells to distal tubule and collecting duct cells[J]. Clinical Biochemistry,2014,47:89-94,2014.
[7]朱迎星,郑萍,赵绍林,等.尿exosomes的分离方法及在临床中应用研究进展[J].中华临床医师杂志(电子版),2016(14):32.
[8]Sharma S,Scholz-Romero K,Rice GE,et al. Methods to Enrich Exosomes from Conditioned Media and Biological Fluids[M].New York:Humana Press,2018:103-115.
[9]Li P,Kaslan M,Lee S H,et al. Progress in exosome isolation techniques[J]. Theranostics,2017,7(3):789.
[10]Luigi Rossi,Maria Celeste Nicoletti,Antonella Di Franco,et al. Urinary excretion of kidney aquaporins as possiblediagnostic biomarker of diabetic nephropathy[J].Journal of Diabetes Research,2017,4360357:13.
[11]Mohan A,Singh RS,Kumari M,et al. Urinary exosomal microRNA-451-5p is a potential early biomarker of diabetic nephropathy in rats[J]. PloS One,2016,11(4):e0154055.
[12]Eissa S,Matboli M,Aboushahba R,et al. Urinary exosomal microRNA panel unravels novel biomarkers for diagnosis of type 2 diabetic kidney disease[J]. Journal of Diabetes and its Complications,2016,30(8):1585-1592.
[13]Denis Deli?,Claudia Eisele,Ramona Schmid,et al. Urinary exosomal miRNA signature in type II diabetic nephropathy patients[J].PLoS One,2016,11(3):1-16.
[14]Zubiri I,Posada-Ayala M,Sanz-Maroto A,et al. Diabetic nephropathy induces changes in the proteome of human urinary exosomes as revealed by label-free comparative analysis[J]. J Proteomics,2014,96:92-102.
[15]Kalani A,Mohan A,Godbole MM,et al. Wilm's tumor-1 protein levels in urinary exosomes from diabetic patients with or without proteinuria[J]. PLoS One,2013,8(3):e60177.
[16]Xiaoming WU,Yanbin GAO. Exosomes from high glucosetreated glomerular endothelial cells activate mesangial cells to promote renal fibrosis[J].Biol Open,2016,5(4):484-491.
[17]WANG YY,TANG LQ,WEI W. Berberine attenuates podocytes injury caused by exosomes derived from high glucose-induced mesangial cells through TGFβ1-PI3K/AKT pathway[J].European Journal of Pharmacology,2018,1:34.
[18]SUN H,YAO W,TANG Y,et al. Urinary exosomes as a novel biomarker for evaluation ofα-lipoic acid's protective effect in early diabetic nephropathy[J]. Journal of Clinical Laboratory Analysis,2017,31(6):22129.
[19]WU S,WANG Z,Bharadwaj S,et al. Implantation of autologous urine derived stem cells expressing vascular endothelial growth factor for potential use in genitourinary reconstruction[J]. The Journal of Urology,2011,186(2):640-647.
[20]ZHANG Y,McNeill E,TIAN H,et al. Urine derived cells are a potential source for urological tissue reconstruction[J]. The Journal of Urology,2008,180(5):2226-2233.
[21]Timmers L,Lim S K,Arslan F,et al. Reduction of myocardial infarct size by human mesenchymal stem cell conditioned medium[J]. Stem Cell Research,2008,1(2):129-137.
[22]JIANG Z,LIU Y,NIU X,et al. Exosomes secreted by human urine-derived stem cells could prevent kidney complications from type I diabetes in rats[J]. Stem Cell Research&Therapy,2016,7(1):24.
[23]PIMPI Khurana R,Ranches G,Schafferer S,et al. Identification of urinary exosomal noncoding RNAs as novel biomarkers in chronic kidney disease[J]. RNA,2017,23(2):142-152.
[24]Lange T,Stracke S,Rettig R,et al. Identification of miR-16 as an endogenous reference gene for the normalization of urinary exosomal miRNA expression data from CKD patients[J].PloS One,2017,12(8):e0183435.
[25]Moon P G,Lee J E,You S,et al. Proteomic analysis of urinary exosomes from patients of early IgA nephropathy and thin basement membrane nephropathy[J]. Proteomics,2011,11(12):2459-2475.
[26]MIN QH,CHEN XM,ZOU YQ,et al. Differential expression of urinary exosomal micro RNA s in IgA nephropathy[J]. Journal of Clinical Laboratory Analysis,2018,32(2):e22226.
[27]FENG Y,LYU L,WU W,et al. Mp351 urinary exosomes and the loading of Ccl2 mrna as biomarker of iga nephropathy patients[J]. Nephrology Dialysis Transplantation,2017,32(suppl_3):555-556.
[28]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]. American Journal of Kidney Diseases,2003,42(3):497-506.
[29]Caglar K,Yilmaz M I,Saglam M,et al. Endothelial dysfunction and fetuin a levels before and after kidney transplantation[J].Transplantation,2007,83(4):392-397.
[30]ZHOU H,Cheruvanky A,HU X,et al. Urinary exosomal transcription factors,a new class of biomarkers for renal disease[J]. Kidney International,2008,74(5):613-621.
[31]Sonoda H,Yokota-Ikeda N,Oshikawa S,et al. Decreased abundance of urinary exosomal aquaporin-1 in renal ischemiareperfusion injury[J]. American Journal of Physiology-Renal Physiology,2009,297(4):F1006-F1016.
[32]YU Y,BAI F,QIN N,et al. Non-proximal renal tubule-derived urinary exosomal miR-200b as a biomarker of renal fibrosis[J].Nephron,2018,10:1159.
[33]HUANG Z,ZHANG Y,ZHOU J,et al. Urinary exosomal miR-193a can be a potential biomarker for the diagnosis of primary focal segmental glomerulosclerosis in children[J]. Bio Med Research International,2017,2017:1115.
[34]Henriett Butzab,Roy Nofech-Mozesa,Qiang Dinga,et al.Exosomal microRNAs are diagnostic biomarkers and can mediate cell-cell communication in renal cell carcinoma[J]. European Urology Focus,2016,2(2):210-218.
[35]De Palma G,Sallustio F,Curci C,et al. The three-gene signature in urinary extracellular vesicles from patients with clear cell renal cell carcinoma[J]. Journal of Cancer,2016,7(14):1960.
[36]Torres V E,Harris P C,Pirson Y. Autosomal dominant polycystic kidney disease[J]. The Lancet,2007,369(9569):1287-1301.
[37]Hogan M C,Manganelli L,Woollard J R,et al. Characterization of PKD protein-positive exosome-like vesicles[J]. Journal of the American Society of Nephrology,2009,20(2):278-288.
[38]Hogan M C,Bakeberg J L,Gainullin V G,et al. Identification of biomarkers for PKD1 using urinary exosomes[J]. Journal of the American Society of Nephrology,2014,16:40354.