Lower urinary tract symptoms (LUTS)—constituting a spectrum disorder that encompasses weak stream, nocturia, and sensations of incomplete emptying and intermittent or hesitant urination—are indicative of lower urinary tract dysfunction (LUTD). LUTD is a progressive disease that can lead to bladder dysfunction if left untreated or treated ineffectively. Sequelae include urinary retention, recurrent UTI, bladder calculi, and, eventually, renal impairment. LUTD involving the prostate is associated with both ageing and inflammation. Tissue inflammation resulting from ageing, infection, or other inflammatory disease processes (for example, type 2 diabetes mellitus) is epidemiologically associated with the subsequent development of tissue fibrosis in multiple organ systems, including the prostate. Recent studies show that tissue fibrosis in the lower urinary tract is associated with LUTD, and suggest that fibrosis might be a previously unrecognized pathobiology that contributes to LUTD. Thus, antifibrotic therapeutic agents should be considered as a new approach to efficaciously treating men with LUTD, especially those who don’t experience durable responses to 5α-reductase inhibitors or α-adrenergic receptor antagonists.

BACKGROUND Progressive aging- and inflammation-associated fibrosis effectively remodels the extracellular matrix (ECM) to increase prostate tissue stiffness and reduce urethral flexibility, resulting in urinary flow obstruction and lower urinary tract symptoms (LUTS). In the current study, we sought to test whether senescence-accelerated mouse prone (SAMP)6 mice, which were reported to develop prostatic fibrosis, would also develop LUTS, and whether these symptoms would be exacerbated by diet-induced obesity and concurrent Type 2 Diabetes Mellitus (T2DM). METHODS To accomplish this, SAMP6 and AKR/J background strain mice were fed regular mouse chow, low fat diet chow, or high fat diet chow for 8 months, then subjected to glucose tolerance tests, assessed for plasma insulin levels, evaluated for urinary voiding function, and assessed for lower urinary tract fibrosis. RESULTS The results of these studies show that SAMP6 mice and AKR/J background strain mice develop diet-induced obesity and T2DM concurrent with urinary voiding dysfunction. Moreover, urinary voiding dysfunction was more severe in SAMP6 than AKR/J mice and was associated with pronounced prostatic and urethral tissue fibrosis. CONCLUSIONS Taken together, these studies suggest that obesity, T2DM, lower urinary tract fibrosis, and urinary voiding dysfunction are inextricably and biologically linked. Prostate.

The aggressive subtype ductal adenocarcinoma is closely related to conventional acinar prostate cancer. Ductal foci contain additional alterations, however, leading to frequent activation of two targetable pathways.