Biology subjects

Bjorling, D. E.

Publications and source records attributed to Bjorling, D. E..

3 recordsLinked to original sources

bioRxiv2020

A Uropathogenic E. coli UTI89 model of prostatic inflammation and collagen accumulation for use in studying aberrant collagen production in the prostate

Bacterial infection is one known etiology of prostatic inflammation. Prostatic inflammation is associated with prostatic collagen accumulation and both are linked to progressive lower urinary tract symptoms in men. We characterized a model of prostatic inflammation utilizing transurethral instillations of E. coli UTI89 in C57BL/6J male mice with the goal of determining the optimal instillation conditions, understanding the impact of instillation conditions on urinary physiology, and identifying ideal prostatic lobes and collagen 1a1 prostatic cell types for further analysis. The smallest instillation volume tested (50 {micro}L) distributes exclusively to bladder, 100 and 200 {micro}L volumes distributes to bladder and prostate, and a 500 {micro}L volume distributes to bladder, prostate and ureter. A threshold optical density (OD) of 0.4 E. coli UTI89 in the instillation fluid is necessary for significant (p < 0.05) prostate colonization. E. coli UTI89 infection results in a low frequency, high volume spontaneous voiding pattern. This phenotype is due to exposure to E. coli UTI89, not catheterization alone, and is minimally altered by a 50 {micro}L increase in instillation volume and doubling of E. coli concentration. Prostate inflammation is isolated to the dorsal prostate and is accompanied by increased collagen density. This is partnered with increased density of PTPRC+, ProCOL1A1+ co-positive cells and decreased density of ACTA2+, ProCOL1A1+ co-positive cells. Overall, we determined that this model is effective in altering urinary phenotype and producing prostatic inflammation and collagen accumulation in mice.

physiology↗

bioRxiv2020

An immunohistochemical prostate cell identification key indicates that aging shifts procollagen 1A1 production from myofibroblasts to fibroblasts in dogs prone to prostate-related urinary dysfunction

Background The identity and spatial distribution of prostatic cell types has been determined in humans but not in dogs, even though aging- and prostate-related voiding disorders are common in both species and mechanistic factors, such as prostatic collagen accumulation, appear to be shared between species. In this publication we characterize the regional distribution of prostatic cell types in the young intact dog to enable comparisons with human and mice and we examine how the cellular source of procollagen 1A1 changes with age in intact male dogs.Methods A multichotomous decision tree involving sequential immunohistochemical stains was validated for use in dog and used to identify specific prostatic cell types and determine their distribution in the capsule, peripheral, periurethral and urethral regions of the young intact canine prostate. Prostatic cells identified using this technique include perivascular smooth muscle cells, pericytes, endothelial cells, luminal, intermediate, and basal epithelial cells, neuroendocrine cells, myofibroblasts, fibroblasts, fibrocytes, and other hematolymphoid cells. Corresponding images were made freely accessible through the GUDMAP database at https://doi.org/10.25548/16-WMM4.Results The prostatic peripheral region harbors the largest proportion of epithelial cells. Aging does not change the density of hematolymphoid cells, fibroblasts, and myofibroblasts in the peripheral region or in the fibromuscular capsule, regions where we previously observed aging- and androgen-mediated increases in prostatic collagen abundance Instead, we observed aging-related changes the procollagen 1A1 positive prostatic cell identity from a myofibroblast to a fibroblast.Conclusions Hematolymphoid cells and myofibroblasts are often identified as sources of collagen in tissues prone to aging-related fibrosis. We show that these are not the likely sources of pathological collagen synthesis in older intact male dogs. Instead, we identify an aging-related shift in the prostatic cell type producing procollagen 1A1 that will help direct development of cell type and prostate appropriate therapeutics for collagen accumulation.View Full Text

pathology↗

bioRxiv2019

Factors Driving Unique Urination Phenotypes of Male and Female 9-week-old C57BL/6J Mice

Laboratory mice are used to identify causes of urinary dysfunction including prostate-related mechanisms of Lower Urinary Tract Symptoms (LUTS). Effective use of mice for this purpose requires a clear understanding of molecular, cellular, anatomical, and endocrine contributions to voiding function. Whether the prostate influences baseline voiding function has not been specifically evaluated, in part because most methods that alter prostate mass also change circulating testosterone concentrations. We performed void spot assay and cystometry to establish a multi-parameter \"baseline\" of voiding function in intact male and female 9-week-old (adult) C57BL/6J mice. We then compared voiding function in intact male mice to that of castrate males, males (and females) treated with the steroid five alpha reductase inhibitor finasteride, or males harboring alleles (Pbsn4cre/+;R26RDta/+) that significantly reduce prostate lobe mass by depleting prostatic luminal epithelial cells. We evaluated aging-related changes in male urinary voiding. We also treated intact male, castrate male, and female mice with exogenous testosterone to determine the influence of androgen on voiding function. The three methods used to reduce prostate mass (castration, finasteride, Pbsn4cre/+; R26RDta/+) changed voiding function from baseline but in a nonuniform manner. Castration feminized some aspects of male urinary physiology (making them more like intact female) while exogenous testosterone masculinized some aspects of female urinary physiology (making them more like intact male). Our results provide evidence that circulating testosterone is responsible in part for baseline sex differences in C57BL/6J mouse voiding function while prostate lobe mass in young, healthy adult mice has a lesser influence.

physiology↗