Broad and diverse roles of sphingosine-1-phosphate/sphingosine-1-phosphate receptors in the prostate
Daoquan Liu,
Jianmin Liu,
Yan Li,
Lu Du,
Qingqiong Cao,
Liang Yang,
Yongying Zhou,
Ping Chen,
Yuming Guo,
Guang Zeng,
Michael E. DiSanto,
Weidong Hu,
Xinhua Zhang
Affiliations
Daoquan Liu
Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Department of Thoracic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Hubei Key Laboratory of Tumor Biological Behaviors & Hubei Provincial Clinical Research Center for Cancer, Wuhan 430071, China
Jianmin Liu
Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
Yan Li
Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
Lu Du
Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
Qingqiong Cao
Department of Ultrasound, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
Liang Yang
Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
Yongying Zhou
Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
Ping Chen
Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
Yuming Guo
Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
Guang Zeng
Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
Michael E. DiSanto
Department of Surgery and Biomedical Sciences, Cooper Medical School of Rowan University, Camden, NJ, USA
Weidong Hu
Department of Thoracic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Hubei Key Laboratory of Tumor Biological Behaviors & Hubei Provincial Clinical Research Center for Cancer, Wuhan 430071, China; Corresponding author
Xinhua Zhang
Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Corresponding author
Summary: Benign prostatic hyperplasia (BPH) is a common condition in aging males, but its underlying pathogenesis remains unclear. Sphingosine-1-phosphate (S1P) and its receptors (S1PRs) play important roles in various diseases, while less studied in prostate. Current study attempts to clarify the expression and functional activities of S1P/S1PRs in the prostate. We discovered that S1P/S1PRs were richly expressed in the prostate, with S1PR1/2/3 localized in the epithelial/stromal compartments, while S1PR4/5 were less expressed. In vitro, S1P/S1PR1/S1PR3 promoted cell proliferation via AKT and ERK1/2 pathways, S1P/S1PR2/S1PR3 enhanced contraction of WPMY-1 cells and human prostate via RhoA/ROCK pathway, while S1P/S1PR1/S1PR2/S1PR3 alleviated the inflammation response via STAT3 pathway. In vivo, S1P and S1PR1/3 agonists (SEW2871, CYM5541) led to prostate enlargement in rats, while S1PR1/3 antagonists (W-146, TY-52156) suppressed testosterone-induced BPH. Overall, this study suggests that S1P/S1PRs play a critical role in the development of BPH and may be a promising therapeutic target for BPH treatment.
