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尿红细胞源性微小RNA:在IgA肾病中的新作用

Urinary Erythrocyte-Derived miRNAs: Emerging Role in IgA Nephropathy.

作者信息

Duan Zhi-Yu, Cai Guang-Yan, Li Ji-Jun, Bu Ru, Chen Xiang-Mei

机构信息

Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, China.

Department of Nephrology, First Affiliated Hospital of Chinese PLA General Hospital, Beijing, China.

出版信息

Kidney Blood Press Res. 2017;42(4):738-748. doi: 10.1159/000481970. Epub 2017 Oct 19.

DOI:10.1159/000481970
PMID:29050002
Abstract

Hematuria is one of the basic clinical manifestations of IgA nephropathy (IgAN). Isolated microscopic hematuria or microscopic hematuria combined with proteinuria is risk factor for the long-term prognosis of IgAN. Current evidence of the consequences of glomerular hematuria rests on insights from basic research on the molecular mechanisms of hemoglobin and related reactive oxygen species-induced tubular injury as well as on the clinical evidence of macroscopic hematuria-associated acute kidney injury (AKI) in IgAN. These researches may simply elucidate some effects of macroscopic hematuria but not microscopic hematuria. Recent studies conducted on blood and urinary erythrocytes have made progress. Researches have revealed that mature erythrocytes contain abundant, long, non-coding RNA, miRNA (microRNA) and Y RNA. Among the top 50 expressions of erythrocyte-derived miRNAs, 33 (66%) of them may be the potential urinary biomarkers of IgAN. Moreover, when urinary erythrocytes are compressed while exiting out of an impaired nephron, erythrocyte-derived vesicles (including microvesicles and apoptotic vesicles) may increase. Animal models for hematuria and human biopsy tissues confirm renal parenchymal cells could phagocytose red blood cells and erythrocyte-derived vesicles. These vesicles, which contain miRNAs, may alter the transcriptome of recipient cells and impact the occurrence and development of IgAN.

摘要

血尿是IgA肾病(IgAN)的基本临床表现之一。孤立性镜下血尿或镜下血尿合并蛋白尿是IgAN长期预后的危险因素。目前关于肾小球血尿后果的证据基于对血红蛋白和相关活性氧诱导肾小管损伤分子机制的基础研究见解,以及IgAN中肉眼血尿相关急性肾损伤(AKI)的临床证据。这些研究可能仅阐明了肉眼血尿的一些影响,而非镜下血尿的影响。最近对血液和尿液红细胞进行的研究取得了进展。研究表明,成熟红细胞含有丰富的长链非编码RNA、微小RNA(miRNA)和Y RNA。在红细胞来源的miRNA的前50种表达中,其中33种(66%)可能是IgAN潜在的尿液生物标志物。此外,当尿液红细胞从受损肾单位排出时受到挤压,红细胞来源的囊泡(包括微泡和凋亡小泡)可能会增加。血尿动物模型和人类活检组织证实肾实质细胞可以吞噬红细胞和红细胞来源的囊泡。这些含有miRNA的囊泡可能会改变受体细胞的转录组,并影响IgAN的发生和发展。

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