Urinary miRNA profiles discriminate between obstruction-induced bladder dysfunction and healthy controls

Siebenthal, Michelle von; Besic, Mustafa; Gheinani, Ali Hashemi; Akshay, Akshay; Lizun-Platoni, Salomé; Kunz, Nadine; Burkhard, Fiona C.; Monastyrskaya, Katia

doi:10.1038/s41598-021-89535-3

Cited by 9 publications

(5 citation statements)

References 48 publications

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“…Our results suggest that total concentration and size are not indicative of either the presence or progression of Fabry nephropathy. In healthy control subjects, the number of uEVs was reported to be higher in younger subjects [ 41 ]. Specific subpopulations of uEVs or the relationship between them may better reflect pathophysiological changes within the kidney than total uEVs [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, the expression of miR-30b-5p increased over the 10-year period, but only in FD patients without nephropathy. A previous study showed no change in miR-30b-5p expression between young and old control subjects [ 41 ]. Although the role of miR-30b-5p in the kidney was only recently discovered, the expression of miR-30b-5p is thought to have a protective role in podocyte injury [ 30 ] and endothelial-to-mesenchymal transition [ 31 ], which are both important stages in the development of nephropathy in FD.…”

Section: Discussionmentioning

confidence: 99%

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Urinary Extracellular Vesicles and Their miRNA Cargo in Patients with Fabry Nephropathy

Levstek

Mlinšek

Holcar

et al. 2021

Genes

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Current biomarkers of Fabry nephropathy lack sensitivity in detecting early kidney damage and do not predict progression of nephropathy. Urinary extracellular vesicles (uEVs) and their molecular cargo could reflect early changes in renal impairment as they are secreted by the cells lining the urinary tract. We aimed to conduct a proof-of-concept study to investigate whether analysis of uEV characteristics and expression of uEV-derived microRNAs (miRNAs) could be applicable in studies to predict the development and progression of nephropathy in Fabry disease. A total of 20 Fabry patients were divided into two groups, depending on the presence of nephropathy. Chronological urine samples collected during 10-year follow-up were used for uEVs isolation with size exclusion chromatography. Nanoparticle tracking analysis was used to determine concentration and size of uEVs. We evaluated the expression of five uEV-derived miRNAs by qPCR (miR-23a-3p, miR-29a-3p, miR-30b-5p, miR-34a-5p, miR-200a-3p). There was no difference in the concentration and size of uEVs between patients with and without nephropathy at last follow-up or longitudinally. However, we found increased expression of miR-29a-3p and miR-200a-3p in uEVs isolated from chronological samples of patients with Fabry nephropathy. This may indicate an attempt by the organism to prevent the progression of renal damage leading to end-stage renal disease as previously reported in type 1 diabetes. In addition, we found an increased expression of miR-30b-5p in the 10-year period in uEVs of patients without renal dysfunction. miR-30b-5 was reported to have a protective role in podocyte injury and may possibly be important in Fabry nephropathy. These findings indicate that uEVs and their molecular cargo could be a promising target of studies focusing on elucidation of Fabry nephropathy. Nevertheless, total concentration and size of uEVs were neither indicative of the presence nor progression of Fabry nephropathy, while the role of the analyzed miRNAs in Fabry nephropathy progression was merely indicated and needs further in-depth studies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Urinary Extracellular Vesicles and Their miRNA Cargo in Patients with Fabry Nephropathy

Levstek

Mlinšek

Holcar

et al. 2021

Genes

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“…Firstly, they have been shown to have valuable diagnostics potential. They can be relatively easily detected and are used as a part of diagnostics criteria [ 280 ]; they have a potential for early cancer detection [ 287 , 288 ], and they can be obtained from both tissues and body fluids, which allows non-invasive early diagnostics [ 289 , 290 , 291 , 292 , 293 ]. Moreover, they can be used as targets in a specific approach in gene therapy.…”

Section: Future Perspectivementioning

confidence: 99%

miRNA in Molecular Diagnostics

et al. 2022

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MicroRNAs are a class of small non-coding RNA molecules that regulate gene expression on post-transcriptional level. Their biogenesis consists of a complex series of sequential processes, and they regulate expression of many genes involved in all cellular processes. Their function is essential for maintaining the homeostasis of a single cell; therefore, their aberrant expression contributes to development and progression of many diseases, especially malignant tumors and viral infections. Moreover, they can be associated with certain states of a specific disease, obtained in the least invasive manner for patients and analyzed with basic molecular methods used in clinical laboratories. Because of this, they have a promising potential to become very useful biomarkers and potential tools in personalized medicine approaches. In this review, miRNAs biogenesis, significance in cancer and infectious diseases, and current available test and methods for their detection are summarized.

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“…The molecular changes in BOO might indicate an increasing involvement of miRNAs in the control of bladder function from the overactive to underactive/acontractile states. Thus, mRNA and miRNA might represent markers of detrusor competence (19,20).…”

Section: Atpmentioning

confidence: 99%

Systematic review of urinary biomarkers of female bladder outlet obstruction (fBOO)

Silva

Dinis²,

Monteiro³

2022

Arch Ital Urol Androl

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Objective: Diagnosis of bladder outlet obstruction (BOO) in females is often challenging, not only because of the overlap in storage and voiding symptoms in women with various etiologies of lower urinary tract (LUT) dysfunction but also due to the lack of standardized urodynamic criteria to define the condition. There is an unmet need of biologic markers to evaluate BOO in females as an adjunct to other clinical criteria. We sought to elucidate the role of urinary biomarkers in female BOO. Material and methods: We performed a systematic review of studies involving urinary biomarkers in female BOO. The search was performed in PubMed. A total of 58 papers were retrieved and 2 were included for final analysis.Results: Currently, there are no validated biologic markers for female BOO available. Having a biomarker that can be obtained through a urine sample will be an invaluable tool to evaluate and counsel patients with LUT symptoms and possible BOO. The use of NGF as an indicator of BOO in female patients seems to be promising: NGF levels are elevated in women with BOO when compared with normal controls. Conclusions: We found that NGF levels may be applied as a useful biomarker in the diagnosis and evaluation of female patients with BOO symptoms. It will not completely replace other clinical diagnostic tools such as formal urodynamic testing but play a role as a supplement to it. Nevertheless, further studies should be conducted to establish NGF levels as a female BOO biomarker and a routine testing modality.

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Urinary miRNA profiles discriminate between obstruction-induced bladder dysfunction and healthy controls

Cited by 9 publications

References 48 publications

Urinary Extracellular Vesicles and Their miRNA Cargo in Patients with Fabry Nephropathy

Urinary Extracellular Vesicles and Their miRNA Cargo in Patients with Fabry Nephropathy

miRNA in Molecular Diagnostics

Systematic review of urinary biomarkers of female bladder outlet obstruction (fBOO)

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