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The signaling pathways and effectors that drive the response of the bladder to nonmalignant insults or injury are incompletely defined. Interrogation of biological systems has been revolutionized by the ability to generate high-content data sets that capture information on a variety of biomolecules in cells and tissues, from DNA to RNA to proteins. In oncology, such an approach has led to the identification of cancer subtypes, improved prognostic capability, and has provided a basis for precision treatment of patients. In contrast, systematic molecular characterization of benign bladder disorders has lagged behind, such that our ability to uncover novel therapeutic interventions or increase our mechanistic understanding of such conditions is limited. Here, we discuss existing literature on the application of omics approaches, including transcriptomics and proteomics, to urinary tract conditions characterized by pathological tissue remodeling. We discuss molecular pathways implicated in remodeling, challenges in the field, and aspirations for omics-based research in the future. [ABSTRACT FROM AUTHOR]

The signaling pathways and effectors that drive the response of the bladder to nonmalignant insults or injury are incompletely defined. Interrogation of biological systems has been revolutionized by the ability to generate high-content data sets that capture information on a variety of biomolecules in cells and tissues, from DNA to RNA to proteins. In oncology, such an approach has led to the identification of cancer subtypes, improved prognostic capability, and has provided a basis for precision treatment of patients. In contrast, systematic molecular characterization of benign bladder disorders has lagged behind, such that our ability to uncover novel therapeutic interventions or increase our mechanistic understanding of such conditions is limited. Here, we discuss existing literature on the application of omics approaches, including transcriptomics and proteomics, to urinary tract conditions characterized by pathological tissue remodeling. We discuss molecular pathways implicated in remodeling, challenges in the field, and aspirations for omics-based research in the future.

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., Competing Interests: None.