Epithelial cells derived exosomal miR-203a-3p facilitates stromal inflammation of type IIIA chronic prostatitis/chronic pelvic pain syndrome by targeting DUSP5 and increasing MCP-1 generation

被引:3
作者
Song, Guojing [1 ]
Zhao, Fuhan [1 ]
Ni, Rongrong [2 ]
Deng, Bingqian [2 ]
Chen, Saipeng [1 ]
Hu, Ruimin [1 ]
Zheng, Jun [1 ]
Peng, Yiji [1 ]
Liu, Heting [2 ]
Luo, Yang [3 ]
Zhou, Zhansong [1 ]
Huang, Gang [2 ]
Shen, Wenhao [1 ]
机构
[1] Army Med Univ, Mil Med Univ 3, Southwest Hosp, Dept Urol, Chongqing 400038, Peoples R China
[2] Army Med Univ, Mil Med Univ 3, Coll Basic Med Sci, Dept Biochem & Mol Biol, Chongqing 400038, Peoples R China
[3] Chongqing Univ, Dept Ctr Smart Lab & Mol Med, Sch Med, Chongqing 400044, Peoples R China
关键词
CP/CPPS-A; Exosomes; miR-203a-3p; DUSP5; Inflammation; EXTRACELLULAR VESICLES; PROSTATE; EXPRESSION; MEDIATORS; KINASES; HEALTH;
D O I
10.1186/s12951-024-02513-5
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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.
引用
收藏
页数:16
相关论文
共 42 条
[1]   Small extracellular vesicles in cancer [J].
Abhange, Komal ;
Makler, Amy ;
Wen, Yi ;
Ramnauth, Natasha ;
Mao, Wenjun ;
Asghar, Waseem ;
Wan, Yuan .
BIOACTIVE MATERIALS, 2021, 6 (11) :3705-3743
[2]   Management of Chronic Prostatitis/Chronic Pelvic Pain Syndrome A Systematic Review and Network Meta-analysis [J].
Anothaisintawee, Thunyarat ;
Attia, John ;
Nickel, J. Curtis ;
Thammakraisorn, Sangsuree ;
Numthavaj, Pawin ;
McEvoy, Mark ;
Thakkinstian, Ammarin .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2011, 305 (01) :78-86
[3]   Mitogen-activated protein kinases in innate immunity [J].
Arthur, J. Simon C. ;
Ley, Steven C. .
NATURE REVIEWS IMMUNOLOGY, 2013, 13 (09) :679-692
[4]   The role of prostatic inflammation biomarkers in the diagnosis of prostate diseases [J].
Bardan, Razvan ;
Dumache, Raluca ;
Dema, Alis ;
Cumpanas, Alin ;
Bucuras, Viorel .
CLINICAL BIOCHEMISTRY, 2014, 47 (10-11) :909-915
[5]   The reactive stroma microenvironment and prostate cancer progression [J].
Barron, David A. ;
Rowley, David R. .
ENDOCRINE-RELATED CANCER, 2012, 19 (06) :R187-R204
[6]   Downregulation of lung miR-203a-3p expression by high-altitude hypoxia enhances VEGF/Notch signaling [J].
Cai, Wei ;
Liu, Sanli ;
Liu, Ziquan ;
Hou, Shike ;
Lv, Qi ;
Cui, Huanhuan ;
Wang, Xue ;
Zhang, Yuxin ;
Fan, Haojun ;
Ding, Hui .
AGING-US, 2020, 12 (05) :4247-4267
[7]   The miR-126-5p and miR-212-3p in the extracellular vesicles activate monocytes in the early stage of radiation-induced vascular inflammation implicated in atherosclerosis [J].
Choi, You Yeon ;
Kim, Areumnuri ;
Lee, Younghyun ;
Lee, Yang Hee ;
Park, Mineon ;
Shin, Eunguk ;
Park, Sunhoo ;
Youn, BuHyun ;
Seong, Ki Moon .
JOURNAL OF EXTRACELLULAR VESICLES, 2023, 12 (05)
[8]   Isolation and characterization of extracellular vesicle subpopulations from tissues [J].
Crescitelli, Rossella ;
Lasser, Cecilia ;
Lotvall, Jan .
NATURE PROTOCOLS, 2021, 16 (03) :1548-+
[9]   The role of the prostatic stroma in chronic prostatitis/chronic pelvic pain syndrome [J].
Dellabella, Marco ;
Milanese, Giulio ;
Sigala, Sandra ;
d'Anzeo, Gianluca ;
Arrighi, Nicola ;
Bodei, Serena ;
Muzzonigro, Giovanni .
INFLAMMATION RESEARCH, 2009, 58 (12) :829-836
[10]   Extracellular vesicles: a rising star for therapeutics and drug delivery [J].
Du, Shuang ;
Guan, Yucheng ;
Xie, Aihua ;
Yan, Zhao ;
Gao, Sijia ;
Li, Weirong ;
Rao, Lang ;
Chen, Xiaojia ;
Chen, Tongkai .
JOURNAL OF NANOBIOTECHNOLOGY, 2023, 21 (01)