Chen Lei, Chen Ziqi, Chen Jia, Du Hexi, Chen Xianguo, Chen Jing, Wang Hui, Liang Chaozhao
Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
Institute of Urology, Anhui Medical University, Hefei, Anhui, China.
Cell Prolif. 2025 Apr;58(4):e13784. doi: 10.1111/cpr.13784. Epub 2024 Dec 24.
The aim is to explore the mechanisms underlying pain development in chronic prostatitis and identify therapeutic targets for pain management in patients with chronic prostatitis. RNA sequence of the spinal cord dorsal horns and proteomic analysis of spinal macrophages of experimental autoimmune prostatitis (EAP) mice were conducted to identify pain-related genes, proteins and signalling pathways. The clodronate liposome, CXCR3 and P-STAT3 inhibitors, NGF antibody and cromolyn sodium were used to investigate the roles of the CXCL10/CXCR3, JAK/STAT3 and NGF/TrKA pathways in spinal macrophage recruitment and pain response. Finally, prostate tissues from benign prostate hyperplasia (BPH) patients were collected to validate the aforementioned results. Neuron and astrocyte-derived CXCL10 was associated with spinal macrophage recruitment, and CXCL10/CXCR3 axis could regulate the chemotaxis of macrophage to the spinal cord in EAP mice. Results of proteomic analysis found that CXCL10 could regulate the JAK/STAT3 pathway to mediate neuroinflammation in EAP, which was validated in vivo and in vitro experiments. The number of mast cells and expressions of NGF, TrKA and PGP9.5 increased in the prostates of EAP mice and BPH patients, and targeting NGF could reduce spinal macrophage recruitment and pain response. NGF was the triggering factor to induce chemotaxis of spinal macrophages and neuroinflammation, and the CXCL10/CXCR3 axis and JAK/STAT3 pathway was involved in spinal macrophage recruitment and infiltration, which provided therapeutic targets for pain management.
目的是探索慢性前列腺炎疼痛发生的潜在机制，并确定慢性前列腺炎患者疼痛管理的治疗靶点。对实验性自身免疫性前列腺炎（EAP）小鼠的脊髓背角进行RNA测序，并对脊髓巨噬细胞进行蛋白质组分析，以确定与疼痛相关的基因、蛋白质和信号通路。使用氯膦酸盐脂质体、CXCR3和P-STAT3抑制剂、NGF抗体和色甘酸钠来研究CXCL10/CXCR3、JAK/STAT3和NGF/TrKA通路在脊髓巨噬细胞募集和疼痛反应中的作用。最后，收集良性前列腺增生（BPH）患者的前列腺组织以验证上述结果。神经元和星形胶质细胞衍生的CXCL10与脊髓巨噬细胞募集有关，CXCL10/CXCR3轴可调节EAP小鼠巨噬细胞向脊髓的趋化作用。蛋白质组分析结果发现，CXCL10可调节JAK/STAT3通路以介导EAP中的神经炎症，这在体内和体外实验中均得到验证。EAP小鼠和BPH患者前列腺中肥大细胞数量以及NGF、TrKA和PGP9.5的表达增加，靶向NGF可减少脊髓巨噬细胞募集和疼痛反应。NGF是诱导脊髓巨噬细胞趋化和神经炎症的触发因素，CXCL10/CXCR3轴和JAK/STAT3通路参与脊髓巨噬细胞的募集和浸润，为疼痛管理提供了治疗靶点。
