Abstract：
Partial bladder outlet obstruction (pBOO) often results in bladder tissue inflammation and remodeling. As human urine-derived stem cells (USCs) have demonstrated therapeutic benefits, we used a rat model to investigate the effect of USCs on bladder function and explore the miRNA and gene expression profiles in bladder tissue using RNA sequencing. Eighteen rats were assigned to a sham surgery group, pBOO group, and pBOO+USC group (six biweekly treatments). Routine urodynamic monitoring, analysis of detrusor muscle strips, and pathophysiology assessments were conducted. Finally, altered miRNA and mRNA expression profiles of bladder tissue were examined using RNA sequencing and bioinformatics analysis. After USC treatment, elevated bladder compliance and maximal voiding pressure, declined end filling pressure and voided volume, and improved detrusor muscle contractility and carbachol sensitivity were found. Histology and TUNEL assay revealed reduced collagen deposition and muscle cell apoptosis in bladder tissue. The differential expression of eight miRNAs was reversed by USC treatment. Two large nodes (miR-142 and miR-9a) were identified in the miRNA-gene interaction network in the USC-treated group. The Kyoto Encyclopedia of Genes and Genomes analysis revealed enrichment of multiple significant pathways, including those involved in necroptosis and cytokine-cytokine receptor interactions. This is the first study to demonstrate the protective effect of USCs on bladder function and remodeling in pBOO rats. The miRNA and mRNA expression levels differed in the bladder of pBOO rats with and without USC treatment. Although the mechanism underlying these effects has not been fully elucidated, necroptosis and cytokine-cytokine receptor interaction-related pathways may be involved.
摘要：
膀胱出口部分梗阻(pBOO)通常导致膀胱组织炎症和重塑。由于人类尿液来源的干细胞（USC）已经证明了治疗益处，我们使用大鼠模型来研究USCs对膀胱功能的影响，并使用RNA测序法探索膀胱组织中的miRNA和基因表达谱。18只大鼠被分配到假手术组，pBOO组,和pBOO+USC组(六个两周治疗)。常规尿动力学监测,逼尿肌肌条分析，并进行病理生理学评估。最后,使用RNA测序和生物信息学分析检查膀胱组织中改变的miRNA和mRNA表达谱。USC治疗后，膀胱顺应性和最大排尿压力升高，最终填充压力和空隙体积下降，发现逼尿肌收缩力和卡巴胆碱敏感性改善。组织学和TUNEL分析显示膀胱组织中胶原蛋白沉积和肌肉细胞凋亡减少。8个miRNAs的差异表达被USC处理逆转。在USC处理组中的miRNA-基因相互作用网络中鉴定出两个大节点(miR-142和miR-9a)。京都基因百科全书和基因组分析揭示了多种重要途径的富集，包括参与坏死性凋亡和细胞因子-细胞因子受体相互作用的那些。这是第一个证明USCs对pBOO大鼠膀胱功能和重塑的保护作用的研究。在有和没有USC治疗的pBOO大鼠的膀胱中miRNA和mRNA表达水平不同。尽管这些影响的潜在机制尚未完全阐明，可能涉及坏死和细胞因子-细胞因子受体相互作用相关通路。
