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.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science

Aging/*physiology ; Fibroblasts/*metabolism ; Myofibroblasts/*metabolism ; Procollagen/*biosynthesis ; Prostate/*cytology ; Urinary Bladder/*physiopathology; Aging/metabolism ; Aging/pathology ; Animals ; Disease Susceptibility ; Dogs ; Immunohistochemistry ; Male ; Prostate/metabolism ; Prostate/pathology

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.
Competing Interests: The authors have declared that no competing interests exist.

Circ Res. 2004 Apr 2;94(6):828-35. (PMID: 14976125)
Mod Pathol. 2009 May;22(5):639-50. (PMID: 19252475)
Nat Rev Immunol. 2011 Jun;11(6):427-35. (PMID: 21597472)
PLoS One. 2013 Apr 22;8(4):e60905. (PMID: 23630575)
Reprod Domest Anim. 2012 Dec;47 Suppl 6:229-31. (PMID: 23279506)
Prostate. 2008 Apr 1;68(5):498-507. (PMID: 18213634)
Theriogenology. 2008 Aug;70(3):375-83. (PMID: 18514299)
J Invest Dermatol. 2007 Mar;127(3):526-37. (PMID: 17299435)
J Cell Biol. 1995 Jul;130(2):393-405. (PMID: 7615639)
Proc Natl Acad Sci U S A. 1996 Apr 30;93(9):4219-23. (PMID: 8633044)
Acta Endocrinol (Copenh). 1958 Feb;27(2):129-39. (PMID: 13497528)
J Clin Invest. 1983 May;71(5):1114-23. (PMID: 6189857)
Am J Surg Pathol. 1988 Aug;12(8):619-33. (PMID: 2456702)
Histol Histopathol. 2000 Jan;15(1):269-80. (PMID: 10668216)
Prostate. 2020 Aug;80(11):872-884. (PMID: 32497356)
Vet Clin North Am Small Anim Pract. 2018 Jul;48(4):701-719. (PMID: 29933768)
PLoS One. 2009 Oct 16;4(10):e7475. (PMID: 19834619)
Cell Mol Life Sci. 2016 Mar;73(6):1145-57. (PMID: 26681260)
PLoS One. 2017 Nov 16;12(11):e0188413. (PMID: 29145476)
Mol Med. 1994 Nov;1(1):71-81. (PMID: 8790603)
J Anat. 2013 Feb;222(2):170-7. (PMID: 23083425)
J Pathol. 2013 Jan;229(2):298-309. (PMID: 22996908)
J Comp Pathol. 1962 Jul;72:321-31. (PMID: 14480921)
Prostate. 2018 Aug;78(11):839-848. (PMID: 29740846)
Urology. 2013 May;81(5):1018-23. (PMID: 23608423)
Nat Methods. 2012 Jun 28;9(7):676-82. (PMID: 22743772)
Virchows Arch. 1994;425(1):3-24. (PMID: 7921410)
Prostate Cancer Prostatic Dis. 2000 Jul;3(1):28-33. (PMID: 12497158)
Am J Respir Crit Care Med. 2005 Apr 15;171(8):899-907. (PMID: 15618458)
Cell Rep. 2018 Dec 18;25(12):3530-3542.e5. (PMID: 30566875)
Methods Mol Biol. 2017;1627:1-23. (PMID: 28836191)
Br J Ophthalmol. 2008 May;92(5):699-704. (PMID: 18441176)
Histochem Cell Biol. 1999 Nov;112(5):387-401. (PMID: 10603079)
Theriogenology. 2016 Mar 15;85(5):835-840. (PMID: 26613854)
PLoS One. 2014 Jun 20;9(6):e100770. (PMID: 24950301)
Fibrogenesis Tissue Repair. 2012 Jun 06;5(Suppl 1):S17. (PMID: 23259769)
Nat Cell Biol. 2013 Mar;15(3):274-83. (PMID: 23434823)

U54 DK104310 United States DK NIDDK NIH HHS; TL1 TR002375 United States TR NCATS NIH HHS; T32 ES007015 United States ES NIEHS NIH HHS; K12 DK100022 United States DK NIDDK NIH HHS; F30 DK122686 United States DK NIDDK NIH HHS; U54 DK100227 United States DK NIDDK NIH HHS; F31 ES028594 United States ES NIEHS NIH HHS

0 (Procollagen)

Date Created: 20200730 Date Completed: 20200908 Latest Revision: 20210609

20240104

PMC7390344

10.1371/journal.pone.0232564

32726309