Aberrant Transforming Growth Factor-β Activation Recruits Mesenchymal Stem Cells During Prostatic Hyperplasia. (7th September 2016)

• Record Type: Journal Article
• Authors: Wang, Long; Xie, Liang; Tintani, Francis; Xie, Hui; Li, Changjun; Cui, Zhuang; Wan, Mei; Zu, Xiongbing; Qi, Lin; Cao, Xu
• Is Part Of: Stem cells translational medicine. Volume 6:Number 2(2017)
• Page Start: 394
• Page End: 404
• Publication Date: 2016-09-07
• Subjects: Benign prostatic hyperplasia -- Transforming growth factor-β -- Mesenchymal stem cells -- Stroma -- Fibrosis; Stem cells -- Periodicals; Regenerative medicine -- Periodicals; Periodicals; 616.0277405
• DOI: 10.5966/sctm.2015-0411
• Languages: English
• ISSNs: 2157-6564

Abstract

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 cells were derived from nestin + cells in Nestin-Cre, Rosa26-YFP flox/+ 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 T β RII in nestin + cell lineage ameliorated stromal hyperplasia. Thus, elevated levels of TGF- β -induced mobilization 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.