Dataset Information

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

ABSTRACT: Urgency, frequency and incomplete emptying are the troublesome symptoms often shared between benign prostatic obstruction-induced (BLUTD) and neurogenic (NLUTD) lower urinary tract dysfunction. Previously, using bladder biopsies, we suggested a panel of miRNA biomarkers for different functional phenotypes of the bladder. Urine is a good source of circulating miRNAs, but sex- and age-matched controls are important for urinary metabolite comparison. In two groups of healthy subjects (average age 32 and 57 years old, respectively) the total protein and RNA content was very similar between age groups, but the number of secreted extracellular vesicles (uEVs) and expression of several miRNAs were higher in the young healthy male volunteers. Timing of urine collection was not important for these parameters. We also evaluated the suitability of urinary miRNAs for non-invasive diagnosis of bladder outlet obstruction (BOO). A three urinary miRNA signature (miR-10a-5p, miR-301b-3p and miR-363-3p) could discriminate between controls and patients with LUTD (BLUTD and NLUTD). This panel of representative miRNAs can be further explored to develop a non-invasive diagnostic test for BOO. The age-related discrepancy in the urinary miRNA content observed in this study points to the importance of selecting appropriate, age-matched controls.

SUBMITTER: von Siebenthal M

PROVIDER: S-EPMC8119692 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

von Siebenthal Michelle M Besic Mustafa M Gheinani Ali Hashemi AH Akshay Akshay A Lizun-Platoni Salomé S Kunz Nadine N Burkhard Fiona C FC Monastyrskaya Katia K

Scientific reports 20210513 1

Urgency, frequency and incomplete emptying are the troublesome symptoms often shared between benign prostatic obstruction-induced (BLUTD) and neurogenic (NLUTD) lower urinary tract dysfunction. Previously, using bladder biopsies, we suggested a panel of miRNA biomarkers for different functional phenotypes of the bladder. Urine is a good source of circulating miRNAs, but sex- and age-matched controls are important for urinary metabolite comparison. In two groups of healthy subjects (average age 3 ...[more]

PMID: 33986358

Similar Datasets

Project description:Disruption of the blood-urine barrier can result in acute or chronic inflammatory bladder injury. Activation of the oxygen-regulated hypoxia-inducible factor (HIF) pathway has been shown to protect mucosal membranes by increasing the expression of cytoprotective genes and by suppressing inflammation. The activity of HIF is controlled by prolyl hydroxylase domain (PHD) dioxygenases, which have been exploited as therapeutic targets for the treatment of anemia of chronic kidney disease. Here, we established a mouse model of acute cyclophosphamide (CYP)-induced blood-urine barrier disruption associated with inflammation and severe urinary dysfunction to investigate the HIF-PHD axis in inflammatory bladder injury. We found that systemic administration of dimethyloxalylglycine or molidustat, two small-molecule inhibitors of HIF-prolyl hydroxylases, profoundly mitigated CYP-induced bladder injury and inflammation as assessed by morphological analysis of transmural edema and urothelial integrity and by measuring tissue cytokine expression. Void spot analysis to examine bladder function quantitatively demonstrated that HIF-prolyl hydroxylase inhibitor administration normalized micturition patterns and protected against CYP-induced alteration of urinary frequency and micturition patterns. Our study highlights the therapeutic potential of HIF-activating small-molecule compounds for the prevention or therapy of bladder injury and urinary dysfunction due to blood-urine barrier disruption.NEW & NOTEWORTHY Disruption of the blood-urine barrier can result in acute or chronic inflammatory bladder injury. Here, we demonstrate that pharmacological inhibition of hypoxia-inducible factor (HIF)-prolyl hydroxylation prevented bladder injury and protected from urinary dysfunction in a mouse model of cyclophosphamide-induced disruption of the blood-urine barrier. Our study highlights a potential role for HIF-activating small-molecule compounds in the prevention or therapy of bladder injury and urinary dysfunction and provides a rationale for future clinical studies.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets