膀胱上皮细胞来源外泌体LncRNA MALAT1通过NLRP3炎症小体调控BOO后膀胱重塑的机制探究

膀胱出口梗阻(BOO)是泌尿系统最常见的疾病之一，BOO继发的膀胱重塑是导致膀胱功能障碍的重要原因，其发病机制尚不清楚。我们前期研究发现，压力可诱导膀胱上皮细胞高表达LncRNA MALAT1，并通过外泌体将其传递至膀胱平滑肌细胞与成纤维细胞，进而促进NLRP3炎症小体激活及胶原的合成与分泌。我们推测，BOO发生后，压力诱导膀胱上皮细胞分泌包含MALAT1的外泌体，这些外泌体可以在膀胱上皮细胞本身及膀胱平滑肌细胞、成纤维细胞等多种细胞层面促进NLRP3炎症小体的激活进而促进膀胱重塑的发生，MALAT1可能是膀胱重塑的生物标志物和治疗靶点。基于此，我们将收集临床样本并结合Nlrp3-/-转基因小鼠动物模型进一步探究MALAT1/NLRP3炎症小体通路调控膀胱重塑的分子机制，并验证尿液中外泌体MALAT1作为膀胱重塑生物标志物的可靠性。本课题的实施将为膀胱重塑提供潜在的生物标记物和防治新靶标。

Bladder outlet obstruction (BOO) is one of the most common diseases in the urinary system. Bladder remodeling secondary to BOO is an important cause of bladder dysfunction. However, its pathogenesis is still unclear. In our previous studies, we found that stress induced high expression of LncRNA MALAT1 in bladder urothelial cells. Then, MALAT1 was packaged into exosomes and transmitted to bladder smooth muscle cells as well as fibroblasts, which promoted the activation of NLRP3 inflammasome and the secretion of collagen. We hypothesize that after BOO, stress-induced bladder urothelial cells release exosomes containing MALAT1, which activate NLRP3 inflammasome in multiple cells like bladder urothelial cells, smooth muscle cells and fibroblasts, leading to bladder remodeling. MALAT1 may act as a biomarker and therapeutic target for bladder remodeling. Therefore, we will collect clinical samples and utilize Nlrp3-/- mice to explore the exact molecular mechanism of MALAT1/NLRP3 pathway in regulating bladder remodeling, and verify the reliability of taking MALAT1 as a biomarker to detect bladder remodeling. This study will help to provide a potential biomarker as well as new treating target of bladder remodeling.