Stromal hyperplasia in male bladders upon loss of transforming growth factor-β signaling in fibroblasts

Ali Reza Sharif-Afshar, Jeffrey M. Donohoe, John C. Pope IV, Mark C. Adams, John W. Brock, Neil A. Bhowmick, Paul F. Austin, Richard Grady, Eric A Kurzrock

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Purpose: Rapid bladder growth associated, partial urethral obstruction and embryonic bladder development entail stromal-epithelial interactions involving signaling by the cytokine transforming growth factor-β (TGF-β). However, to our knowledge the role of TGF-β in bladder stromal hyperplasia and hypertrophy is not understood. Materials and Methods: In an effort to understand the specific role of TGF-β signaling in bladder stroma a fibroblast specific conditional knockout mouse of the type II TGF-β receptor gene, Tgfbr2/spko, was generated using Cre-lox methodology. Bladders from 18, 7 to 8-week-old mice were harvested for histological and immunohistochemical analysis. Results: Bladders from homozygous Tgfbr2/ spko male mice showed marked hypertrophy in the lamina propria and smooth muscle layers in the absence of visible or functional bladder obstruction by age 8 weeks. However, age matched female mice of the same genotype maintained bladder architecture similar to that in wild-type littermate male and female controls. Immunohistochemistry for the phosphorylated form of Smad2 indicated a general loss in TGF-β signaling in the lamina propria of bladders of male and female Tgfbr2/spko mice, and yet pronounced α-smooth muscle actin expression was noted in male Tgfbr2/spko bladders, which is a marker for myofibroblasts. Conclusions: A sex disparity was observed in the Tgfbr2/spko mouse model lacking TGF-β signaling in fibroblasts. Deletion of TGF-β in males leads to a hypertrophied lamina propria and muscularis externa with myofibroblast differentiation and proliferation. Female homozygous Tgfbr2/spko bladders appeared the same as those of wild-type male and female controls. This model suggests a role for stromal TGF-β signaling with estrogens and androgens in bladder fibrosis.

Original languageEnglish (US)
Pages (from-to)1704-1707
Number of pages4
JournalJournal of Urology
Volume174
Issue number4 II
DOIs
StatePublished - Oct 2005

Fingerprint

Transforming Growth Factors
Hyperplasia
Urinary Bladder
Fibroblasts
Mucous Membrane
Myofibroblasts
Hypertrophy
Smooth Muscle
Urethral Obstruction
Growth Factor Receptors
Knockout Mice
Androgens
Embryonic Development
Actins
Estrogens
Fibrosis
Immunohistochemistry
Genotype
Cytokines

Keywords

  • Bladder
  • Fibroblast
  • Tgf-beta
  • Transgenic mice

ASJC Scopus subject areas

  • Urology

Cite this

Sharif-Afshar, A. R., Donohoe, J. M., Pope IV, J. C., Adams, M. C., Brock, J. W., Bhowmick, N. A., ... Kurzrock, E. A. (2005). Stromal hyperplasia in male bladders upon loss of transforming growth factor-β signaling in fibroblasts. Journal of Urology, 174(4 II), 1704-1707. https://doi.org/10.1097/01.ju.0000164720.72732.9c

Stromal hyperplasia in male bladders upon loss of transforming growth factor-β signaling in fibroblasts. / Sharif-Afshar, Ali Reza; Donohoe, Jeffrey M.; Pope IV, John C.; Adams, Mark C.; Brock, John W.; Bhowmick, Neil A.; Austin, Paul F.; Grady, Richard; Kurzrock, Eric A.

In: Journal of Urology, Vol. 174, No. 4 II, 10.2005, p. 1704-1707.

Research output: Contribution to journalArticle

Sharif-Afshar, AR, Donohoe, JM, Pope IV, JC, Adams, MC, Brock, JW, Bhowmick, NA, Austin, PF, Grady, R & Kurzrock, EA 2005, 'Stromal hyperplasia in male bladders upon loss of transforming growth factor-β signaling in fibroblasts', Journal of Urology, vol. 174, no. 4 II, pp. 1704-1707. https://doi.org/10.1097/01.ju.0000164720.72732.9c
Sharif-Afshar AR, Donohoe JM, Pope IV JC, Adams MC, Brock JW, Bhowmick NA et al. Stromal hyperplasia in male bladders upon loss of transforming growth factor-β signaling in fibroblasts. Journal of Urology. 2005 Oct;174(4 II):1704-1707. https://doi.org/10.1097/01.ju.0000164720.72732.9c
Sharif-Afshar, Ali Reza ; Donohoe, Jeffrey M. ; Pope IV, John C. ; Adams, Mark C. ; Brock, John W. ; Bhowmick, Neil A. ; Austin, Paul F. ; Grady, Richard ; Kurzrock, Eric A. / Stromal hyperplasia in male bladders upon loss of transforming growth factor-β signaling in fibroblasts. In: Journal of Urology. 2005 ; Vol. 174, No. 4 II. pp. 1704-1707.
@article{420b564e500a4e22920bb9a4eeebecad,
title = "Stromal hyperplasia in male bladders upon loss of transforming growth factor-β signaling in fibroblasts",
abstract = "Purpose: Rapid bladder growth associated, partial urethral obstruction and embryonic bladder development entail stromal-epithelial interactions involving signaling by the cytokine transforming growth factor-β (TGF-β). However, to our knowledge the role of TGF-β in bladder stromal hyperplasia and hypertrophy is not understood. Materials and Methods: In an effort to understand the specific role of TGF-β signaling in bladder stroma a fibroblast specific conditional knockout mouse of the type II TGF-β receptor gene, Tgfbr2/spko, was generated using Cre-lox methodology. Bladders from 18, 7 to 8-week-old mice were harvested for histological and immunohistochemical analysis. Results: Bladders from homozygous Tgfbr2/ spko male mice showed marked hypertrophy in the lamina propria and smooth muscle layers in the absence of visible or functional bladder obstruction by age 8 weeks. However, age matched female mice of the same genotype maintained bladder architecture similar to that in wild-type littermate male and female controls. Immunohistochemistry for the phosphorylated form of Smad2 indicated a general loss in TGF-β signaling in the lamina propria of bladders of male and female Tgfbr2/spko mice, and yet pronounced α-smooth muscle actin expression was noted in male Tgfbr2/spko bladders, which is a marker for myofibroblasts. Conclusions: A sex disparity was observed in the Tgfbr2/spko mouse model lacking TGF-β signaling in fibroblasts. Deletion of TGF-β in males leads to a hypertrophied lamina propria and muscularis externa with myofibroblast differentiation and proliferation. Female homozygous Tgfbr2/spko bladders appeared the same as those of wild-type male and female controls. This model suggests a role for stromal TGF-β signaling with estrogens and androgens in bladder fibrosis.",
keywords = "Bladder, Fibroblast, Tgf-beta, Transgenic mice",
author = "Sharif-Afshar, {Ali Reza} and Donohoe, {Jeffrey M.} and {Pope IV}, {John C.} and Adams, {Mark C.} and Brock, {John W.} and Bhowmick, {Neil A.} and Austin, {Paul F.} and Richard Grady and Kurzrock, {Eric A}",
year = "2005",
month = "10",
doi = "10.1097/01.ju.0000164720.72732.9c",
language = "English (US)",
volume = "174",
pages = "1704--1707",
journal = "Journal of Urology",
issn = "0022-5347",
publisher = "Elsevier Inc.",
number = "4 II",

}

TY - JOUR

T1 - Stromal hyperplasia in male bladders upon loss of transforming growth factor-β signaling in fibroblasts

AU - Sharif-Afshar, Ali Reza

AU - Donohoe, Jeffrey M.

AU - Pope IV, John C.

AU - Adams, Mark C.

AU - Brock, John W.

AU - Bhowmick, Neil A.

AU - Austin, Paul F.

AU - Grady, Richard

AU - Kurzrock, Eric A

PY - 2005/10

Y1 - 2005/10

N2 - Purpose: Rapid bladder growth associated, partial urethral obstruction and embryonic bladder development entail stromal-epithelial interactions involving signaling by the cytokine transforming growth factor-β (TGF-β). However, to our knowledge the role of TGF-β in bladder stromal hyperplasia and hypertrophy is not understood. Materials and Methods: In an effort to understand the specific role of TGF-β signaling in bladder stroma a fibroblast specific conditional knockout mouse of the type II TGF-β receptor gene, Tgfbr2/spko, was generated using Cre-lox methodology. Bladders from 18, 7 to 8-week-old mice were harvested for histological and immunohistochemical analysis. Results: Bladders from homozygous Tgfbr2/ spko male mice showed marked hypertrophy in the lamina propria and smooth muscle layers in the absence of visible or functional bladder obstruction by age 8 weeks. However, age matched female mice of the same genotype maintained bladder architecture similar to that in wild-type littermate male and female controls. Immunohistochemistry for the phosphorylated form of Smad2 indicated a general loss in TGF-β signaling in the lamina propria of bladders of male and female Tgfbr2/spko mice, and yet pronounced α-smooth muscle actin expression was noted in male Tgfbr2/spko bladders, which is a marker for myofibroblasts. Conclusions: A sex disparity was observed in the Tgfbr2/spko mouse model lacking TGF-β signaling in fibroblasts. Deletion of TGF-β in males leads to a hypertrophied lamina propria and muscularis externa with myofibroblast differentiation and proliferation. Female homozygous Tgfbr2/spko bladders appeared the same as those of wild-type male and female controls. This model suggests a role for stromal TGF-β signaling with estrogens and androgens in bladder fibrosis.

AB - Purpose: Rapid bladder growth associated, partial urethral obstruction and embryonic bladder development entail stromal-epithelial interactions involving signaling by the cytokine transforming growth factor-β (TGF-β). However, to our knowledge the role of TGF-β in bladder stromal hyperplasia and hypertrophy is not understood. Materials and Methods: In an effort to understand the specific role of TGF-β signaling in bladder stroma a fibroblast specific conditional knockout mouse of the type II TGF-β receptor gene, Tgfbr2/spko, was generated using Cre-lox methodology. Bladders from 18, 7 to 8-week-old mice were harvested for histological and immunohistochemical analysis. Results: Bladders from homozygous Tgfbr2/ spko male mice showed marked hypertrophy in the lamina propria and smooth muscle layers in the absence of visible or functional bladder obstruction by age 8 weeks. However, age matched female mice of the same genotype maintained bladder architecture similar to that in wild-type littermate male and female controls. Immunohistochemistry for the phosphorylated form of Smad2 indicated a general loss in TGF-β signaling in the lamina propria of bladders of male and female Tgfbr2/spko mice, and yet pronounced α-smooth muscle actin expression was noted in male Tgfbr2/spko bladders, which is a marker for myofibroblasts. Conclusions: A sex disparity was observed in the Tgfbr2/spko mouse model lacking TGF-β signaling in fibroblasts. Deletion of TGF-β in males leads to a hypertrophied lamina propria and muscularis externa with myofibroblast differentiation and proliferation. Female homozygous Tgfbr2/spko bladders appeared the same as those of wild-type male and female controls. This model suggests a role for stromal TGF-β signaling with estrogens and androgens in bladder fibrosis.

KW - Bladder

KW - Fibroblast

KW - Tgf-beta

KW - Transgenic mice

UR - http://www.scopus.com/inward/record.url?scp=24944584062&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=24944584062&partnerID=8YFLogxK

U2 - 10.1097/01.ju.0000164720.72732.9c

DO - 10.1097/01.ju.0000164720.72732.9c

M3 - Article

C2 - 16148686

AN - SCOPUS:24944584062

VL - 174

SP - 1704

EP - 1707

JO - Journal of Urology

JF - Journal of Urology

SN - 0022-5347

IS - 4 II

ER -