Zhu Sheng, Wang Yi-Yi, Hu Xin-Yue, Zhou Hong-Liang, Wang Guang, Chen Hui-Xiang, Zeng Hong-Bo, Xie Hui, Wang Zhen-Xing, Xu Ran
Department of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Hunan Key Laboratory of Angmedicine, Changsha, Hunan 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan 410008, China.
Department of Urology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
Int Immunopharmacol. 2025 Mar 6;149:114195. doi: 10.1016/j.intimp.2025.114195. Epub 2025 Feb 3.
Cigarette smoking (CS) is a well-known risk factor for inducing prostate inflammation and fibrosis, presenting significant threats to male reproductive health. Recent research has highlighted the significant role of gut microbiota (GM) in regulating extra-intestinal organs. This study aimed to investigate the effects of Akk and its extracellular vesicles (EVs) on CS-induced prostate inflammation and fibrosis.
This study utilized a mouse model of mainstream smoke exposure to investigate the effects of Akkermansia muciniphila (Akk) and its EVs on prostate tissue affected by CS. Prostate inflammation and fibrosis was assessed through HE staining, qRT-PCR, IHC staining, and immunofluorescence staining. Functional protein P9 enriched in Akk-EVs was used to intervene cigarette smoke extract (CSE)-exposed BPH-1 cells in vitro to validate the anti-inflammatory and anti-fibrotic effects.
The results revealed that CS exposure leads or led to pronounced prostatic inflammation and fibrosis, accompanied by a notable decrease in intestinal levels of Akk. Supplementation with Akk was found to effectively mitigate prostate lesions caused by CS, with the therapeutic effects primarily attributed to the Akk-derived extracellular vesicles (Akk-EVs). The transport kinetics of Akk-EVs to prostate tissue and cells were elucidated, providing insights into their mechanism of action. Both in vitro and in vivo experiments demonstrated that Akk-EVs and their enriched P9 protein effectively ameliorated CS-induced pro-inflammatory cytokine expression and collagen deposition in the prostate.
These findings highlight the anti-inflammatory and anti-fibrotic properties of Akk-EVs and P9 protein, suggesting their potential as therapeutic agents for CS-induced prostate lesions.
吸烟是诱发前列腺炎症和纤维化的众所周知的危险因素，对男性生殖健康构成重大威胁。最近的研究强调了肠道微生物群（GM）在调节肠外器官方面的重要作用。本研究旨在探讨嗜黏蛋白阿克曼氏菌（Akk）及其细胞外囊泡（EVs）对吸烟诱导的前列腺炎症和纤维化的影响。
本研究利用主流烟雾暴露小鼠模型，研究嗜黏蛋白阿克曼氏菌（Akk）及其细胞外囊泡对受吸烟影响的前列腺组织的作用。通过苏木精-伊红（HE）染色、定量逆转录聚合酶链反应（qRT-PCR）、免疫组化（IHC）染色和免疫荧光染色评估前列腺炎症和纤维化。用富含于Akk-EVs中的功能蛋白P9在体外干预暴露于香烟烟雾提取物（CSE）的BPH-1细胞，以验证其抗炎和抗纤维化作用。
结果显示，吸烟导致前列腺明显的炎症和纤维化，同时肠道中Akk水平显著降低。发现补充Akk可有效减轻吸烟引起的前列腺损伤，其治疗效果主要归因于Akk衍生的细胞外囊泡（Akk-EVs）。阐明了Akk-EVs向前列腺组织和细胞的转运动力学，为其作用机制提供了见解。体外和体内实验均表明，Akk-EVs及其富集的P9蛋白有效改善了吸烟诱导的前列腺促炎细胞因子表达和胶原沉积。
这些发现突出了Akk-EVs和P9蛋白的抗炎和抗纤维化特性，表明它们作为吸烟诱导的前列腺损伤治疗剂的潜力。
