Concordant miRNA and mRNA expression profiles in humans and mice with bladder outlet obstruction.

Hashemi Gheinani, Ali; Köck, Ivonne; Vasquez, Evalynn; Baumgartner, Ulrich; Bigger-Allen, Alexander; Sack, Bryan S; Burkhard, Fiona C.; Adam, Rosalyn M; Monastyrskaya, Katia (2018). Concordant miRNA and mRNA expression profiles in humans and mice with bladder outlet obstruction. American journal of clinical and experimental urology, 6(6), pp. 219-233. e-Century Publishing

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Bladder outlet obstruction (BOO) leads to lower urinary tract symptoms (LUTS) and urodynamic changes of the bladder function. Previously we identified microRNA (miRNA) and mRNA expression profiles associated with different states of BOO-induced LUTD in human patients. Bladder wall remodeling resulting from obstruction is widely studied in animal models of experimentally-induced partial BOO (pBOO). Here we determined the expression profiles of miRNAs and selected mRNAs in pBOO mice and compared the observed changes to human patients. Similar to results from human patients, we observed a down-regulation of smooth muscle-associated miRNAs mmu-miR-1, mmu-miR-143, mmu-miR-145, mmu-miR-486 and mmu-miR-133a in pBOO mouse bladders. Pro-fibrotic miRNAs mmu-miR-142-3p and mmu-miR-21 were up-regulated, and anti-fibrotic miRNA mmu-miR-29c was down-regulated. Pathway analysis in human BOO patients identified TNF-alpha as the top upstream regulator. Although there was evidence of hypertrophic changes in pBOO mice, contrary to human data, we observed no regulation of TNF-responsive genes in the mouse model. Experimentally-induced pBOO in mice led to significant gene expression changes, including alteration of pro-fibrotic mRNAs and miRNAs resembling human BOO patients. Gene expression changes were also validated in a mouse model of bladder inflammation. Lack of evidence of TNF-alpha-induced miRNA and mRNA regulation might indicate a different pathophysiological mechanism of organ remodeling in pBOO model compared to the human disease.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Urologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Urologie

04 Faculty of Medicine > Service Sector > Institute of Pathology > Tumour Pathology
04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Urology

UniBE Contributor:

Hashemi Gheinani, Ali; Köck, Ivonne; Baumgartner, Ulrich; Burkhard, Fiona and Monastyrskaya-Stäuber, Katia

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2330-1910

Publisher:

e-Century Publishing

Language:

English

Submitter:

Jeannine Wiemann

Date Deposited:

09 Mar 2020 15:17

Last Modified:

09 Mar 2020 15:17

PubMed ID:

30697578

Uncontrolled Keywords:

Lower urinary tract symptoms fibrosis partial bladder outlet obstruction pathway analysis

BORIS DOI:

10.7892/boris.141106

URI:

https://boris.unibe.ch/id/eprint/141106

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