PDF(Pubmed)
Abstract：
Increased proinflammatory cytokines and infiltration of inflammatory cells in the stroma are important pathological features of type IIIA chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS-A), and the interaction between stromal cells and other cells in the inflammatory microenvironment is closely related to the inflammatory process of CP/CPPS-A. However, the interaction between stromal and epithelial cells remains unclear. In this study, inflammatory prostate epithelial cells (PECs) released miR-203a-3p-rich exosomes and facilitated prostate stromal cells (PSCs) inflammation by upregulating MCP-1 expression. Mechanistically, DUSP5 was identified as a novel target gene of miR-203a-3p and regulated PSCs inflammation through the ERK1/2/MCP-1 signaling pathway. Meanwhile, the effect of exosomes derived from prostatic fluids of CP/CPPS-A patients was consistent with that of exosomes derived from inflammatory PECs. Importantly, we demonstrated that miR-203a-3p antagomirs-loaded exosomes derived from PECs targeted the prostate and alleviated prostatitis by inhibiting the DUSP5-ERK1/2 pathway. Collectively, our findings provide new insights into underlying the interaction between PECs and PSCs in CP/CPPS-A, providing a promising therapeutic strategy for CP/CPPS-A.
摘要：
促炎细胞因子的增多和基质中炎性细胞的浸润是IIIA型慢性前列腺炎/慢性盆腔痛综合征(CP/CPPS-A)的重要病理特点,炎症微环境中基质细胞与其他细胞的相互作用与CP/CPPS-A的炎症过程密切相关。然而,基质细胞和上皮细胞之间的相互作用尚不清楚.在这项研究中,炎性前列腺上皮细胞（PECs）释放富含miR-203a-3p的外泌体，并通过上调MCP-1表达促进前列腺基质细胞（PSC）炎症。机械上,DUSP5被鉴定为miR-203a-3p的新靶基因，并通过ERK1/2/MCP-1信号通路调节PSC炎症。同时,CP/CPPS-A患者前列腺液外泌体的作用与炎性PEC外泌体的作用一致.重要的是,我们证明,来自PECs的miR-203a-3pantagomir负载外泌体靶向前列腺,并通过抑制DUSP5-ERK1/2通路缓解前列腺炎.总的来说，我们的发现为CP/CPPS-A中PEC和PSC之间的相互作用提供了新的见解，为CP/CPPS-A提供有希望的治疗策略
