Prostatic collagen architecture in neutered and intact canines

Ruetten, Hannah; Wegner, Kyle A; Romero, Michael F.; Wood, Michael W.; Marker, Paul C.; Strand, Douglas W.; Colopy, Sara A.; Vezina, Chad M.

doi:10.1002/pros.23641

Cited by 13 publications

(24 citation statements)

References 32 publications

(62 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We defined them by dividing the glandular region into two concentric rings of equal thickness. Our approach led to the discovery that the peripheral and periurethral regions differ in epithelial and stromal cell composition (Figure 1 and 3) and propensity to develop aging-related collagen accumulation[12]. Our results support the notion that peripheral and periurethral region microenvironments uniquely regulate cell behavior and cell composition and may even confer differences in aging-related pathology, much as the human prostate transition and peripheral zones differ in susceptibility to benign hyperplasia and cancer.…”

Section: Discussionsupporting

confidence: 71%

“…We previously identified an aging- and androgen-dependent increase in prostatic collagen density in the prostatic capsule and peripheral regions of intact male canines. [12] Here we test the hypothesis that aging increases myofibroblast density in these canine prostate regions.…”

Section: Resultsmentioning

confidence: 99%

“…[1–11] Human and dog prostates organize into distinct anatomical zones with an externally bound fibromuscular capsule (anatomical features not shared by the mouse prostate). [12] Careful histological and molecular analyses of human prostate have revolutionized our understanding of the cell types of the prostate, revealing a gland that contains at least five epithelial cell types and three fibroblast-like stromal cell types that are organized into three zones. [13, 14] Canine prostate cell types and their spatial distribution across the gland have not been extensively examined using modern molecular and multiplex immunohistochemical methods.…”

Section: Introductionmentioning

confidence: 99%

“…We previously used whole transverse sections of canine prostate to map aging- and castration-mediated changes in prostatic collagen architecture. [12] We found that aging increases collagen fiber thickness and density in the capsule and peripheral regions of intact dogs susceptible to prostatism. [12] Numerous studies across multiple organ systems have identified myofibroblasts as fibrosis inducing cell types.…”

Section: Introductionmentioning

confidence: 99%

“…[12] We found that aging increases collagen fiber thickness and density in the capsule and peripheral regions of intact dogs susceptible to prostatism. [12] Numerous studies across multiple organ systems have identified myofibroblasts as fibrosis inducing cell types. [15–20] The second goal of this study is to test if myofibroblast populations expand and produce pro-collagen type 1A1 in the regions of the canine prostate prone to aging related collagen accumulation.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

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

Ruetten

Cole

Wehber

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

34Background: The identity and spatial distribution of prostatic cell types has been 35 determined in humans but not in dogs, even though aging-and prostate-related voiding 36 disorders are common in both species and mechanistic factors, such as prostatic collagen 37 accumulation, appear to be shared between species. In this publication we characterize 38 the regional distribution of prostatic cell types in the young intact dog to enable 39 comparisons with human and mice and we examine how the cellular source of 40 procollagen 1A1 changes with age in intact male dogs. 41Methods: A multichotomous decision tree involving sequential immunohistochemical 42 stains was validated for use in dog and used to identify specific prostatic cell types and 43 determine their distribution in the capsule, peripheral, periurethral and urethral regions of 44 the young intact canine prostate. Prostatic cells identified using this technique include 45 perivascular smooth muscle cells, pericytes, endothelial cells, luminal, intermediate, and 46 basal epithelial cells, neuroendocrine cells, myofibroblasts, fibroblasts, fibrocytes, and 47 other hematolymphoid cells. Corresponding images were made freely accessible through 48 the GUDMAP database at https://doi.org/10.25548/16-WMM4. 49 Results: The prostatic peripheral region harbors the largest proportion of epithelial cells. 50 Aging does not change the density of hematolymphoid cells, fibroblasts, and 51 myofibroblasts in the peripheral region or in the fibromuscular capsule, regions where we 52 previously observed aging-and androgen-mediated increases in prostatic collagen 53 abundance Instead, we observed aging-related changes the procollagen 1A1 positive 54 prostatic cell identity from a myofibroblast to a fibroblast. 55 Conclusions: Hematolymphoid cells and myofibroblasts are often identified as sources 56 of collagen in tissues prone to aging-related fibrosis. We show that these are not the likely 57 sources of pathological collagen synthesis in older intact male dogs. Instead, we identify 58 an aging-related shift in the prostatic cell type producing procollagen 1A1 that will help 59 direct development of cell type and prostate appropriate therapeutics for collagen 60 accumulation. 61 62 Keywords: fibrosis, BPH, Collagen, LUTS 63 64 1. Introduction 65 Men and dogs develop prostatic disorders spontaneously and in an aging-and 66 androgen-dependent fashion.[1-11] Human and dog prostates organize into distinct 67 anatomical zones with an externally bound fibromuscular capsule (anatomical features 68 not shared by the mouse prostate).[12] Careful histological and molecular analyses of 69 human prostate have revolutionized our understanding of the cell types of the prostate, 70revealing a gland that contains at least five epithelial cell types and three fibroblast-like 71 stromal cell types that are organized into three zones. [13, 14] Canine prostate cell types 72 and their spatial distribution across the gland have not been extensively examined using 73 modern molecular a...

show abstract

Section: Discussionsupporting

confidence: 71%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Ruetten

Cole

Wehber

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

Prostate epithelial‐specific expression of activated PI3K drives stromal collagen production and accumulation

Wegner

Mueller

Unterberger

et al. 2019

The Journal of Pathology

Self Cite

View full text Add to dashboard Cite

We genetically engineered expression of an activated form of P110 alpha, the catalytic subunit of PI3K, in mouse prostate epithelium to create a mouse model of direct PI3K activation (Pbsn-cre4Prb;PI3K GOF/+). We hypothesized that direct activation would cause rapid neoplasia and cancer progression. Pbsn-cre4Prb;PI3K GOF/+ mice developed widespread prostate intraepithelial hyperplasia, but stromal invasion was limited and overall progression was slower than anticipated. However, the model produced profound and progressive stromal remodeling prior to explicit epithelial neoplasia. Increased stromal cellularity and inflammatory infiltrate were evident as early as 4 months of age and progressively increased through 12 months of age, the terminal endpoint of this study. Prostatic collagen density and phosphorylated SMAD2-positive prostatic stromal cells were expansive and accumulated with age, consistent with pro-fibrotic TGF- pathway activation. Few reported mouse models accumulate prostate-specific collagen to the degree observed in Pbsn-cre4Prb;PI3K GOF/+. Our results indicate a signaling process beginning with prostatic epithelial PI3K and TGF- signaling that drives prostatic stromal hypertrophy and collagen accumulation. These mice afford a unique opportunity to explore molecular mechanisms of prostatic collagen accumulation that is relevant to cancer progression, metastasis, inflammation and urinary dysfunction.

show abstract

Relevance of dog as an animal model for urologic diseases

Ruetten

Vezina

2022

Progress in Molecular Biology and Translational Science

View full text Add to dashboard Cite

Prostatic collagen architecture in neutered and intact canines

Abstract: Collagen architecture in dog appears similar to that in humans when cross sections are compared side-by-side. Canine collagen organization is affected by both age and androgen status, suggesting these factors may contribute to collagen accumulation in some males.

Cited by 13 publications

References 32 publications

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

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

Prostate epithelial‐specific expression of activated PI3K drives stromal collagen production and accumulation

Relevance of dog as an animal model for urologic diseases

Contact Info

Product

Resources

About