炎症影响基底前列腺干细胞中的雄激素受体信号传递,通过互白素1受体对手
Paula O Cooper1,2,3, Jiang Yang1,2,3, Hsing-Hui Wang1,2,3
1Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907, USA.
Research square
|January 3, 2024
概括
在良性前列腺增生症 (BPH) 中的慢性炎症通过增强的雄激素受体 (AR) 活性,由介素-1受体对抗剂 (IL-1RA) 介导,驱动前列腺干细胞 (bPSC) 的增殖和分化. 这一发现揭示了导致BPH的新机制.
科学领域:
- 泌尿器科 泌尿器科 泌尿器科 泌尿器科
- 炎症研究 炎症研究
- 干细胞生物学 干细胞生物学
背景情况:
- 良性前列腺增生 (BPH) 通常与慢性前列腺炎症有关,但将炎症与前列腺扩大和症状联系在一起的潜在机制尚不清楚.
- 炎症在BPH发病过程中的作用,特别是它对前列腺干细胞的影响,需要进一步研究.
研究的目的:
- 阐明慢性炎症影响基本前列腺干细胞 (bPSC) 行为的机制,并导致前列腺增生.
- 确定参与炎症驱动的bPSC增殖和分化中的关键分子调节者.
主要方法:
- 使用前列腺卵白蛋白表达转基因3 (POET3) 鼠标模型模仿慢性前列腺炎.
- 采用有机体培养和血统追踪来研究bPSC在炎症和割条件下的行为.
- 研究了雄激素受体 (AR) 信号传导和IL-1RA在炎症bPSC中的作用.
主要成果:
- 在POET3小鼠中的炎症导致炎症细胞增加,促炎细胞因子增加,随后发生表皮和脑膜增生.
- 炎症的bPSC表现出增强的AR活性,这对于它们在有机培养物中的分化至关重要.
- 鉴定出interleukin 1受体对抗剂 (IL-1RA) 是一个关键的调解剂,对抗IL-1α并增强bPSC中的AR信号传递.
- 炎症诱导了bPSC的增殖和分化为光细胞,即使在缺乏雄激素的条件下,突出了炎症驱动的AR激活.
结论:
- 慢性炎症通过增强bPSC中的AR活性来促进前列腺增生,从而导致其增殖和分化.
- IL-1RA在调解炎症对bPSCs中AR信号传递的影响方面发挥着关键作用.
- 这些发现揭示了新的机制,通过调节干细胞行为和AR信号,将炎症与BPH病原体联系起来.
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