Abstract
Benign prostatic hyperplasia (BPH) is the overgrowth of prostate tissues with high prevalence in older men. BPH pathogenesis is not completely understood, but it is believed to be a result of de novo overgrowth of prostatic stroma. In this study, we show that aberrant activation of transforming growth factor-β(TGF-β)mobilizes mesenchymal/stromal stem cells (MSCs) in circulating blood, which are recruited for the prostatic stromal hyperplasia. Elevated levels of active TGF-β were observed in both a phenylephrine-induced prostatic hyperplasia mouse model and human BPH tissues. Nestin lineage tracing revealed that 39.6% ± 6.3% of fibroblasts and 73.3% ± 4.2% smooth muscle cellswere derived fromnestin+ cells in Nestin-Cre, Rosa26-YFPflox/+ mice. Nestin+ MSCs were increased in the prostatic hyperplasia mice. Our parabiosis experiment demonstrate that nestin+ MSCs were mobilized and recruited to the prostatic stroma of wild-type mice and gave rise to the fibroblasts. Moreover, injection of a TGF-β neutralizing antibody (1D11) inhibits mobilization of MSCs, their recruitment to the prostatic stroma and hyperplasia. Importantly, knockout of TbRII in nestin+ cell lineage ameliorated stromal hyperplasia. Thus, elevated levels of TGF-β-inducedmobilization and recruitment of MSCs to the reactive stroma resulting in overgrowth of prostate tissues in BPH and, thus, inhibition of TGF-β activity could be a potential therapy for BPH.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 394-404 |
| Number of pages | 11 |
| Journal | Stem cells translational medicine |
| Volume | 6 |
| Issue number | 2 |
| DOIs | |
| State | Published - Feb 1 2017 |
Fingerprint
Keywords
- Benign prostatic hyperplasia
- Fibrosis
- Mesenchymal stem cells
- Stroma
- Transforming growth factor-β
ASJC Scopus subject areas
- Developmental Biology
- Cell Biology
Cite this
Aberrant transforming growth factor-β activation recruits Mesenchymal stem cells during prostatic hyperplasia. / Wang, Long; Xie, Liang; Tintani, Francis; Xie, Hui; Li, Changjun; Cui, Zhuang; Wan, Mei; Zu, Xiongbing; Qi, Lin; Cao, Xu.
In: Stem cells translational medicine, Vol. 6, No. 2, 01.02.2017, p. 394-404.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Aberrant transforming growth factor-β activation recruits Mesenchymal stem cells during prostatic hyperplasia
AU - Wang, Long
AU - Xie, Liang
AU - Tintani, Francis
AU - Xie, Hui
AU - Li, Changjun
AU - Cui, Zhuang
AU - Wan, Mei
AU - Zu, Xiongbing
AU - Qi, Lin
AU - Cao, Xu
PY - 2017/2/1
Y1 - 2017/2/1
N2 - Benign prostatic hyperplasia (BPH) is the overgrowth of prostate tissues with high prevalence in older men. BPH pathogenesis is not completely understood, but it is believed to be a result of de novo overgrowth of prostatic stroma. In this study, we show that aberrant activation of transforming growth factor-β(TGF-β)mobilizes mesenchymal/stromal stem cells (MSCs) in circulating blood, which are recruited for the prostatic stromal hyperplasia. Elevated levels of active TGF-β were observed in both a phenylephrine-induced prostatic hyperplasia mouse model and human BPH tissues. Nestin lineage tracing revealed that 39.6% ± 6.3% of fibroblasts and 73.3% ± 4.2% smooth muscle cellswere derived fromnestin+ cells in Nestin-Cre, Rosa26-YFPflox/+ mice. Nestin+ MSCs were increased in the prostatic hyperplasia mice. Our parabiosis experiment demonstrate that nestin+ MSCs were mobilized and recruited to the prostatic stroma of wild-type mice and gave rise to the fibroblasts. Moreover, injection of a TGF-β neutralizing antibody (1D11) inhibits mobilization of MSCs, their recruitment to the prostatic stroma and hyperplasia. Importantly, knockout of TbRII in nestin+ cell lineage ameliorated stromal hyperplasia. Thus, elevated levels of TGF-β-inducedmobilization and recruitment of MSCs to the reactive stroma resulting in overgrowth of prostate tissues in BPH and, thus, inhibition of TGF-β activity could be a potential therapy for BPH.
AB - Benign prostatic hyperplasia (BPH) is the overgrowth of prostate tissues with high prevalence in older men. BPH pathogenesis is not completely understood, but it is believed to be a result of de novo overgrowth of prostatic stroma. In this study, we show that aberrant activation of transforming growth factor-β(TGF-β)mobilizes mesenchymal/stromal stem cells (MSCs) in circulating blood, which are recruited for the prostatic stromal hyperplasia. Elevated levels of active TGF-β were observed in both a phenylephrine-induced prostatic hyperplasia mouse model and human BPH tissues. Nestin lineage tracing revealed that 39.6% ± 6.3% of fibroblasts and 73.3% ± 4.2% smooth muscle cellswere derived fromnestin+ cells in Nestin-Cre, Rosa26-YFPflox/+ mice. Nestin+ MSCs were increased in the prostatic hyperplasia mice. Our parabiosis experiment demonstrate that nestin+ MSCs were mobilized and recruited to the prostatic stroma of wild-type mice and gave rise to the fibroblasts. Moreover, injection of a TGF-β neutralizing antibody (1D11) inhibits mobilization of MSCs, their recruitment to the prostatic stroma and hyperplasia. Importantly, knockout of TbRII in nestin+ cell lineage ameliorated stromal hyperplasia. Thus, elevated levels of TGF-β-inducedmobilization and recruitment of MSCs to the reactive stroma resulting in overgrowth of prostate tissues in BPH and, thus, inhibition of TGF-β activity could be a potential therapy for BPH.
KW - Benign prostatic hyperplasia
KW - Fibrosis
KW - Mesenchymal stem cells
KW - Stroma
KW - Transforming growth factor-β
UR - http://www.scopus.com/inward/record.url?scp=85017608542&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85017608542&partnerID=8YFLogxK
U2 - 10.5966/sctm.2015-0411
DO - 10.5966/sctm.2015-0411
M3 - Article
C2 - 28191756
AN - SCOPUS:85017608542
VL - 6
SP - 394
EP - 404
JO - Stem cells translational medicine
JF - Stem cells translational medicine
SN - 2157-6564
IS - 2
ER -