多肽REPDM促进细胞再上皮化在阴道黏膜感染与防御中的作用及机制研究

阴道感染性疾病是困扰女性的常见疾病，“抗菌-黏膜修复-恢复阴道微生态平衡”为治疗领域的最新发展趋势，其中黏膜修复（复层鳞状上皮细胞周期性更新）是阴道防御感染的重要机制，也是防治阴道感染的共性环节与关键步骤。REPDM是通过质谱筛选获得、在最常见阴道感染性疾病（BV）患者阴道分泌物中低表达、功能未知的内源性多肽。前期发现，REPDM可促进阴道上皮细胞再上皮化（增殖-迁移-分化），增加细胞脱落而减少细菌粘附；Pull Down揭示MMP-7为其靶标，免疫荧光实验证实两者存在胞内共定位，REPDM可诱导MMP-7表达增加。提示REPDM通过上调MMP-7，促进上皮细胞再上皮化，增强黏膜自我更新而防御感染及维持阴道微生态平衡。本研究拟全面评估REPDM功能；系统论证“REPDM-MMP-7-阴道上皮细胞再上皮化”机制。如成功，有望丰富阴道黏膜感染与防御的机制，为阴道感染性疾病治疗提供新靶标和线索。

Vaginal infections are common diseases that afflict women. "Antibacterial treatment-mucous rehabilitation-vaginal microecological balance restoring" is the latest development trend in the field of treatment, of which mucosal rehabilitation (periodic updates of stratified squamous epithelial cells) is one of the important mechanisms to defend against vaginal infections. Besides, it is the common link and key steps of preventing and treating vaginal infection. REPDM belongs to a kind of endogenous polypeptide with unknown function, which has low expression in vaginal discharge of bacterial vaginosis (BV) patients by mass spectrometry. Previous studies have found that REPDM could accelerate re-epithelialization (proliferation-migration-differentiation) of vaginal epithelial cells to increase cell shedding and reduce bacterial adhesion; MMP-7 was revealed as its target by Pull Down, and the immunofluorescence experiment confirmed them had intracellular co-localization, and REPDM could induce increased expression of MMP-7. It prompts that REPDM could defense against infection and maintain vaginal microecological balance by upregulating MMP-7, accelerating re-epithelialization of epithelial cells and strengthening mucosa renewal. This research attempted to comprehensively assess the function of REPDM, and systematically demonstrate the mechanism of “REPDM-MMP-7-re-epithelialization of vaginal epithelial cells”. This research was hopeful to enrich common knowledge of infection and defense of vaginal mucosa. Furthermore, it could provide new target for therapy of vaginal infectious diseases, as well as new clue for other infectious diseases, which both have great original innovation.