间质性膀胱炎/膀胱疼痛综合症（IC/BPS）病因复杂，疗效不佳，亟待研究。国外学者及我们证实AKT通路活化所致膀胱平滑肌细胞自噬活性降低，炎症增强是IC/BPS发病的重要机制。申请人运用人尿源干细胞（hUSCs）干预IC/BPS发现其具有较好的抗炎作用，hUSCs可溶性蛋白S100A9可活化RAGE受体上调PTEN蛋白，阻断AKT信号，增强自噬，降低炎症，但具体机制不清。现有研究提示心肌素相关转录因子（MRTF-A）活化后进入细胞核，与早期生长反应因子（Egr1）形成复合体，可能是RAGE受体调控PTEN表达的主要途径。基于此，我们拟通过系列实验，观察MTRF-A/Egr1复合体形成对细胞自噬的影响，证明其调控PTEN基因表达的作用位点，并在体干预MTRF-A/Egr1复合体，观察hUSCs对IC/BPS自噬和炎症的影响。本研究将为探索和改进hUSCs作为IC/BPS治疗策略奠定理论基础。

Interstitial cystitis/bladder pain syndrome (IC/BPS) is of complex etiology and poor efficacy. Studying the pathogenesis mechanism is valuable for clinical treatment. Foreign scholars and we have confirmed that the uncontrollable inflammation response due to autophagy level increasing induced by activating AKT pathway is the most important mechanism in IC/BPS pathophysiological process. In previous studies, we have attempted to explore the role of human urine derived stem cell (hUSCs) and found that hUSCs play an anti-inflammatory effect in IC/BPS rat model. The hUSCs soluble protein, S100A9 can up-regulate PTEN protein through binding and activating RAGE receptor, to activate autophagy and reduce inflammation by blocking AKT signal pathway. but the specific molecular mechanism is unclear. Existing studies suggest that the activated myocardin-related transcription factor (MRTF-A) can transfer into the nucleus and form a transcriptional complex with early growth response factor (Egr1), which may be the main pathway for RAGE receptor regulation of PTEN. Based on this, we intend to design a series of experiments to observe the effect of MTRF-A/Egr1 complex on the autophagy level, and prove its role in regulating the expression of PTEN gene, and intervene the MTRF-A/Egr1 complex in IC/BPS animal model to observe the therapeutic effects of hUSCs on autophagy and inflammation in IC/BPS. This study will provide the theoretical foundation for investigating hUSCs as an treatment strategy for IC/BPS, and improving the therapeutic effects.