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

Abstract

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...