miR-199a-5p regulates urothelial permeability and may play a role in bladder pain syndrome

Monastyrskaya, Katia; Sánchez-Freire, Verónica; Hashemi Gheinani, Ali; Klumpp, David J; Babiychuk, Eduard B; Draeger, Annette; Burkhard, Fiona C (2013). miR-199a-5p regulates urothelial permeability and may play a role in bladder pain syndrome. American journal of pathology, 182(2), pp. 431-48. New York, N.Y.: Elsevier 10.1016/j.ajpath.2012.10.020

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Defects in urothelial integrity resulting in leakage and activation of underlying sensory nerves are potential causative factors of bladder pain syndrome, a clinical syndrome of pelvic pain and urinary urgency/frequency in the absence of a specific cause. Herein, we identified the microRNA miR-199a-5p as an important regulator of intercellular junctions. On overexpression in urothelial cells, it impairs correct tight junction formation and leads to increased permeability. miR-199a-5p directly targets mRNAs encoding LIN7C, ARHGAP12, PALS1, RND1, and PVRL1 and attenuates their expression levels to a similar extent. Using laser microdissection, we showed that miR-199a-5p is predominantly expressed in bladder smooth muscle but that it is also detected in mature bladder urothelium and primary urothelial cultures. In the urothelium, its expression can be up-regulated after activation of cAMP signaling pathways. While validating miR-199a-5p targets, we delineated novel functions of LIN7C and ARHGAP12 in urothelial integrity and confirmed the essential role of PALS1 in establishing and maintaining urothelial polarity and junction assembly. The present results point to a possible link between miR-199a-5p expression and the control of urothelial permeability in bladder pain syndrome. Up-regulation of miR-199a-5p and concomitant down-regulation of its multiple targets might be detrimental to the establishment of a tight urothelial barrier, leading to chronic pain.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Urology
UniBE Contributor:	Burkhard, Fiona Christine
ISSN:	0002-9440
Publisher:	Elsevier
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 14:38
Last Modified:	02 Mar 2023 23:21
Publisher DOI:	10.1016/j.ajpath.2012.10.020
PubMed ID:	23201090
Web of Science ID:	000314486800017
URI:	https://boris.unibe.ch/id/eprint/15445 (FactScience: 222791)