MicroRNAs may mediate the down-regulation of neurokinin-1 receptor in chronic bladder pain syndrome

Sanchez Freire, Veronica; Burkhard, Fiona C; Kessler, Thomas M; Kuhn, Annette; Draeger, Annette; Monastyrskaya, Katia (2010). MicroRNAs may mediate the down-regulation of neurokinin-1 receptor in chronic bladder pain syndrome. American journal of pathology, 176(1), pp. 288-303. New York, N.Y.: Elsevier 10.2353/ajpath.2010.090552

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Bladder pain syndrome (BPS) is a clinical syndrome of pelvic pain and urinary urgency-frequency in the absence of a specific cause. Investigating the expression levels of genes involved in the regulation of epithelial permeability, bladder contractility, and inflammation, we show that neurokinin (NK)1 and NK2 tachykinin receptors were significantly down-regulated in BPS patients. Tight junction proteins zona occludens-1, junctional adherins molecule -1, and occludin were similarly down-regulated, implicating increased urothelial permeability, whereas bradykinin B(1) receptor, cannabinoid receptor CB1 and muscarinic receptors M3-M5 were up-regulated. Using cell-based models, we show that prolonged exposure of NK1R to substance P caused a decrease of NK1R mRNA levels and a concomitant increase of regulatory micro(mi)RNAs miR-449b and miR-500. In the biopsies of BPS patients, the same miRNAs were significantly increased, suggesting that BPS promotes an attenuation of NK1R synthesis via activation of specific miRNAs. We confirm this hypothesis by identifying 31 differentially expressed miRNAs in BPS patients and demonstrate a direct correlation between miR-449b, miR-500, miR-328, and miR-320 and a down-regulation of NK1R mRNA and/or protein levels. Our findings further the knowledge of the molecular mechanisms of BPS, and have relevance for other clinical conditions involving the NK1 receptor.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy > Cell Biology
04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Urology
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Gynaecology
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy

UniBE Contributor:

Sanchez Freire, Veronica; Burkhard, Fiona C.; Kessler, Thomas M.; Kuhn, Annette; Draeger, Annette and Monastyrskaya-Stäuber, Katia

ISSN:

0002-9440

Publisher:

Elsevier

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:07

Last Modified:

06 Dec 2013 13:19

Publisher DOI:

10.2353/ajpath.2010.090552

PubMed ID:

20008142

Web of Science ID:

000274111200030

URI:

https://boris.unibe.ch/id/eprint/121 (FactScience: 196219)

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