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

American Journal of Clinical and Experimental Urology

Alex¹  Ivonne Köck²  Ali Hashemi Gheinani³  Fiona C Burkhard⁴  er Bigger-Allen⁵  Bryan S Sack⁶  Ulrich Baumgartner⁷  Evalynn Vasquez⁸ 

[1] Biological and Biomedical Sciences PhD Program, Harvard Medical School, Boston, MA, USA;Department of Surgery, Harvard Medical School, Boston, MA, USA;Department of Urology, Boston Childrens Hospital, Boston, MA, USA;Department of Urology, Mott Childrens Hospital and University of Michigan, Ann Arbor, MI 48109, USA;Department of Urology, University Hospital, Bern, Switzerland;Division of Urology, Childrens Hospital Los Angeles and Keck School of Medicine of the University of Southern California, Los Angeles, CA 90027, USA;Institute of Pathology, University of Bern, Switzerland;Urology Research Laboratory, Department of Clinical Research, University of Bern, Switzerland

关键词: Lower urinary tract symptoms;    partial bladder outlet obstruction;    fibrosis;    pathway analysis;   

DOI  :  

学科分类：医学（综合）

来源: e-Century Publishing Corporation

【 摘 要 】

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.

【 授权许可】

CC BY-NC