MicroRNA expression profile of urinary exosomes in Type IV lupus nephritis complicated by cellular crescent

Li, Yang; Xu, Xiaosong; Tang, Xiao-Peng; Bian, Xiu‐Wu; Shen, Bingbing; Zhao, Hongwen; Luo, Shiyuan; Chen, Zhiwen; Zhang, Ke‐Qin

doi:10.1186/s40709-018-0088-0

Cited by 26 publications

(25 citation statements)

References 34 publications

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“…7,8 The gold standard for diagnosis is an invasive renal biopsy, but this process could result in serious complications of variable severity and cannot be performed frequently in patients with DM. 9 Therefore, screening for specific and sensitive biomarkers is urgently needed for the early diagnosis of DKD and long-term monitoring of progression to ESRD.…”

Section: Introductionmentioning

confidence: 99%

<p>Alpha1-Antitrypsin in Urinary Extracellular Vesicles: A Potential Biomarker of Diabetic Kidney Disease Prior to Microalbuminuria</p>

Ning¹,

Xiang²,

Xiong³

et al. 2020

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Purpose: Diabetic kidney disease (DKD), which is related to inflammation and immune response, is the primary vascular complication of diabetes mellitus and also the leading etiology of end-stage renal disease. Urinary extracellular vesicles (UEVs) are an attractive source for biomarker detection as they involve molecular constituents derived from their parental sections of the nephron. In this study, we aimed to search for a potential biomarker in UEVs for the early diagnosis and prediction of DKD, especially before the emergence of microalbuminuria. Patients and Methods: UEVs were isolated from the urine of healthy subjects, prediabetic, and diabetic patients with varying degrees of kidney damage by ultracentrifugation, and the extracted UEVs were used to measure alpha1-antitrypsin (α1-AT) by Western blot. To explore the function of α1-AT in the inflammatory process leading to DKD, we silenced the expression of α1-AT in renal tubular epithelial cells using cell transfection techniques to assess the differential expression of the inflammatory factors such as MCP-1 and TNF-α using qRT-PCR. Results: There was no expression of α1-AT in the UEVs of either healthy or pre-diabetic subjects. Its expression was significantly increased in the UEVs of diabetic patients with normoalbuminuria (prior to microalbuminuria), which was more sensitive and more stable than other renal indexes to predict DKD. Additionally, the expression of α1-AT in UEVs was gradually upregulated with the aggravation of DKD and the decline of renal function. In vitro, the mRNA expression of MCP-1 and TNF-α was significantly decreased when the generation of α1-AT in tubular epithelial cells was inhibited under high glucose stimulation. Conclusion: Our results suggest that α1-AT derived from UEVs, especially in diabetic patients with normoalbuminuria, might serve as a potential noninvasive biomarker for diagnosis of DKD early in the development of the disease and may predict the future decline of renal function.

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Section: Introductionmentioning

confidence: 99%

<p>Alpha1-Antitrypsin in Urinary Extracellular Vesicles: A Potential Biomarker of Diabetic Kidney Disease Prior to Microalbuminuria</p>

Ning¹,

Xiang²,

Xiong³

et al. 2020

DMSO

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“…Lupus nephritis is characterized by downregulation of urinary exosomal miR-29c [ 77 ] and upregulation of miR-146a [ 78 ], miR-150, and miR-21 [ 77 ]. A decrease in miR-21 along with let-7a miRNA precursor may indicate disease flare [ 79 ]; an increase in urinary exosomal miR-3135b, miR-654-5p, and miR-146a-5p has been described in cellular crescent formation of lupus nephritis [ 80 ]. Conversely, higher urinary exosomal levels of miR-31, miR-107, and miR-135b-5p are associated with a better response to treatment [ 81 ].…”

Section: Resultsmentioning

confidence: 99%

Exosomes in Nephropathies: A Rich Source of Novel Biomarkers

et al. 2020

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The biomarkers commonly utilized in diagnostic evaluations of kidney disease suffer from low sensitivity, especially in the early stages of renal damage. On the other hand, obtaining a renal biopsy to augment clinical decision making can lead to potentially serious complications. In order to overcome the shortcomings of currently available diagnostic tools, recent studies suggest that exosomes, cell-secreted extracellular vesicles containing a large array of active molecules to facilitate cell-to-cell communication, may represent a rich source of novel disease biomarkers. Because of their endocytic origin, exosomes carry markers typical for their parent cells, which could permit the localization of biochemical cellular alterations in specific kidney compartments. Different types of exosomes can be isolated from noninvasively obtained biofluids; however, in the context of kidney disease, evidence has emerged on the role of urinary exosomes in the diagnostic and predictive modeling of renal pathology. The current review summarizes the potential application of exosomes in the detection of acute and chronic inflammatory, metabolic, degenerative, and genetic renal diseases.

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“…Similarly, the anti-inflammatory miRNAs (i.e., let-7a and miR-21) were down-regulated in urinary exosomes derived from patients with LN and might serve as the non-invasive biomarkers to classify the clinical stage of LN (Tangtanatakul et al, 2019). Furthermore, urinary exosomal miR-3135b was increased in patients with active LN class IV as compared to those with inactive LN class IV and healthy controls, whereas miR-654-5p was increased only in LN class IV with cellular crescent (with very poor prognosis) (Li et al, 2018b). For other glomerular diseases, a previous study using a proteomics approach has shown that urinary exosomal aminopeptidase N, vasorin precursor, a-1-antitrypsin, and ceruloplasmin could differentiate immunoglobulin A (IgA) nephropathy from thin basement membrane nephropathy and healthy controls (Moon et al, 2011).…”

Section: Lupus Nephritis and Other Glomerular Diseasesmentioning

confidence: 97%