Activation of common signaling pathways during remodeling of the heart and the bladder

Abstract

The heart and the urinary bladder are hollow muscular organs, which can be afflicted by pressure overload injury due to pathological conditions such as hypertension and bladder outlet obstruction. This increased outflow resistance induces hypertrophy, marked by dramatic changes in the organs' phenotype and function. The end result in both the heart and the bladder can be acute organ failure due to advanced fibrosis and the subsequent loss of contractility. There is emerging evidence that microRNAs (miRNAs) play an important role in the pathogenesis of heart failure and bladder dysfunction. MiRNAs are endogenous non-coding single-stranded RNAs, which regulate gene expression and control adaptive and maladaptive organ remodeling processes. This Review summarizes the current knowledge of molecular alterations in the heart and the bladder and highlights common signaling pathways and regulatory events. The miRNA expression analysis and experimental target validation done in the heart provide a valuable source of information for investigators working on the bladder and other organs undergoing the process of fibrotic remodeling. Aberrantly expressed miRNA are amendable to pharmacological manipulation, offering an opportunity for development of new therapies for cardiac and bladder hypertrophy and failure.

Characterization of miRNA-regulated networks, hubs of signaling, and biomarkers in obstruction-induced bladder dysfunction

“…Here, we report quantitative transcriptome and miRNA profiling using biopsy samples from human patients with different states of urodynamically defined BOO-induced bladder dysfunction. Our results correspond well with those of previous studies in animal models of partial BOO (pBOO) and cardiac hypertrophy (19) and point to the similarity of mechanisms underlying organ remodeling during pressure overload.…”

“…Normalized Ct values for 3-mRNA or 3-miRNA signatures of the samples with the known urodynamic status ( Figure 5, E and F) were employed in machine-based learning algorithms described in the Methods to train the model. Using the Ct values for either mRNA or miRNA signatures of the blinded samples as an input, the model allocated them to 3 groups corresponding to the predicted bladder functional state: BOO7, 24, 31, 32, 37, 38, 39, 40, 6, 5, 21, 22 and 23 belonged to the DO group; BOO16, 14, 15, 9, 8, 33, and 34 belonged to the BO group, and the remaining samples (BOO28, 29,30,41,42,10,11,12,13,17,18,19,20,4,3,2,1,25,26,27) were from the UA group. On the heatmaps, the samples were colored according to the machine-based group allocation (DO in blue, BO in green, and UA in orange) ( Figure 6, A and B).…”

Novel findings continue to challenge researchers and clinicians

“…Similarities in pressure-overload-induced remodelling of the heart and bladder include changes in microRNA expression that influence tissue permeability, stiffness and smooth muscle differentiation, indicating novel therapeutic targets 1 …”

“…Current management strategies used in the treatment of hypertension might provide a model to improve the treatment paradigm in bladder dysfunction 1 . Both heart and bladder undergo repeated cycles of filling and contraction and respond to pathological pressure overload by developing hypertrophy and fibrosis, eventually resulting in dysfunction.…”

“…A review by Koek et al 1 published in 2015 summarizes common signalling pathways the role of miRNAs. These small, noncoding, single-stranded RNAs regulate gene expression by a post-transcriptional mechanism and have critical functions in cell proliferation, differentiation and death.…”