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

Hannah Ruetten, Clara Cole, Marlyse Wehber, Kyle A. Wegner, Nicholas M. Girardi, Nelson T. Peterson, Brandon R. Scharpf, Michael F. Romero, Michael W. Wood, Sara A. Colopy, Dale E. Bjorling, Chad M. Vezina

Research output: Contribution to journalArticle

Abstract

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. To enhance rigor and transparency, all high resolution images (representative images shown in the figures and biological replicates) are available 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.

Original languageEnglish (US)
Article numbere0232564
JournalPloS one
Volume15
Issue number7 July
DOIs
StatePublished - Jul 2020

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Ruetten, H., Cole, C., Wehber, M., Wegner, K. A., Girardi, N. M., Peterson, N. T., Scharpf, B. R., Romero, M. F., Wood, M. W., Colopy, S. A., Bjorling, D. E., & Vezina, C. M. (2020). 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. PloS one, 15(7 July), [e0232564]. https://doi.org/10.1371/journal.pone.0232564