LINC00664作为ceRNA在慢性前列腺炎介导阴茎海绵体平滑肌细胞表型转化及内皮细胞功能失调的分子机制

Chronic prostatitis (CP/CPPS) usually cause structural and functional abnormalities of the corpus cavernosum ,but the mechanism remains unclear. The ceRNA mechanism is a new mode of gene expression regulation that plays a key role in a variety of physiological and disease states,but it has not been reported in CP/CPPS. Our previous study found: ①The expression of IL-1β increased in CP/ CPPS patients succus prostaticus and blood; ②CP/CPPS may damage the smooth muscle cells and endothelial cells.The next pre-experiment found that: ①In CP/CPPS rat model, the IL-1β increased may lead to decreased mir-145,increased LINC00664 and disturb Wnt signaling pathway; ②By bioinformatics analysis, mir-145 and LINC00664 may form ceRNA. Therefore, our group made assumptions that in CP / CPPS, the IL-1β elevated promotes the formation of ceRNA in LINC00664 and mir-145, which interferes with the Wnt signaling pathway, then regulating the phenotypic transformation of vascular smooth muscle cells and endothelial cell function in the corpus cavernosum. In view of this, this project is intended to conduct a comprehensive study both in vivo and in vitro and provide a new strategy for the treatment of structural and functional abnormalities of the corpus cavernosum caused by CP / CPPS.

慢性前列腺炎(CP/CPPS)可导致阴茎海绵体结构和功能异常，但机制不明。ceRNA机制是一种全新的基因表达调控模式，但在CP/CPPS方面未见报道。我们前期研究发现：①CP/CPPS患者前列腺液及血液中IL-1β表达增高；②CP/CPPS可能损害阴茎海绵体平滑肌和内皮细胞功能。进一步预实验发现：①在CP/CPPS大鼠模型中，IL-1β升高可能导致mir-145降低，LINC00664升高，Wnt信号通路异常。②通过生物信息学分析，mir-145和LINC00664可能形成ceRNA。因此，本课题组提出假设：在CP/CPPS中，IL-1β升高促进LINC00664和mir-145形成ceRNA，干扰Wnt信号通路，进而调节阴茎海绵体血管平滑肌表型转化及内皮细胞功能变化。鉴于此，本项目拟从体内和体外水平全面研究，为治疗CP/CPPS导致的阴茎海绵体结构和功能异常提供新策略。

慢性前列腺炎(CP/CPPS)可导致阴茎海绵体结构和功能异常，但机制不明。我们前期研究发现：①CP/CPPS患者 前列腺液及血液中IL-1β表达增高；②CP/CPPS可能损害阴茎海绵体平滑肌和内皮细胞功能。进一步预实验发现：①在CP/CPPS大鼠模型中，IL-1β升高可能导致mir-145降低，Wnt信号通路异常。.项目主要结果如下：1、我们对阴茎组织进行原代细胞提取，成功获得了EAP大鼠原代平滑肌细胞与内皮细胞。2、通过EAP大鼠原代平滑肌细胞以及正常大鼠平滑肌细胞进行全基因组测序，确定差异表达的miR-145-5p在正常大鼠平滑肌细胞中高表达，而在EAP大鼠平滑肌细胞中低表达。3、阐明miR-145-5p-NF-KB信号通路在慢性前列腺炎介导的阴茎海绵体表型转化的作用机制。4、在此基础上，形成以mir-145-KLF5为核心的研究，为防治慢性前列腺炎导致的阴茎海绵体结构和功能障碍提出新的靶点和思路。