Broad and diverse roles of sphingosine-1-phosphate/sphingosine-1-phosphate receptors in the prostate

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub Date : 2024-10-30 DOI:10.1016/j.isci.2024.111290

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

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Abstract

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.

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鞘氨醇-1-磷酸/鞘氨醇-1-磷酸受体在前列腺中的广泛而多样的作用

良性前列腺增生症（BPH）是老年男性的常见病，但其潜在的发病机制仍不清楚。两性鞘氨醇-1-磷酸（S1P）及其受体（S1PRs）在多种疾病中发挥着重要作用，但对前列腺的研究较少。本研究试图阐明 S1P/S1PRs 在前列腺中的表达和功能活动。我们发现 S1P/S1PRs 在前列腺中表达丰富，其中 S1PR1/2/3 定位于上皮/基质区，而 S1PR4/5 则表达较少。在体外，S1P/S1PR1/S1PR3 通过 AKT 和 ERK1/2 途径促进细胞增殖，S1P/S1PR2/S1PR3 通过 RhoA/ROCK 途径增强 WPMY-1 细胞和人类前列腺的收缩，而 S1P/S1PR1/S1PR2/S1PR3 则通过 STAT3 途径减轻炎症反应。在体内，S1P 和 S1PR1/3 激动剂（SEW2871、CYM5541）会导致大鼠前列腺增生，而 S1PR1/3 拮抗剂（W-146、TY-52156）会抑制睾酮诱导的良性前列腺增生。总之，这项研究表明，S1P/S1PRs 在良性前列腺增生症的发病过程中起着关键作用，可能是治疗良性前列腺增生症的一个有前途的治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

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