尿源干细胞通过FGF2-PI3K/mTOR通路抑制内皮细胞过度自噬治疗糖尿病性勃起功能障碍的机制研究

糖尿病性勃起功能障碍（DED）发病率高且疗效不佳，其核心发病机制是阴茎海绵窦内皮功能障碍。我们前期研究证实细胞过度自噬是海绵窦内皮功能障碍的重要机制，并首次证明尿源干细胞（USCs）可改善DED大鼠的内皮功能和勃起功能，但具体机制未明。进一步预实验发现USCs旁分泌成纤维细胞生长因子2（FGF2）可抑制海绵窦内皮细胞自噬，可能与PI3K/Akt/mTOR通路有关。因此我们提出USCs通过旁分泌FGF2激活PI3K/Akt/mTOR通路抑制内皮细胞过度自噬，从而修复DED大鼠内皮功能和勃起功能的科学假设。本项目拟通过体外共培养、基因芯片和反向蛋白芯片等技术获得FGF2激活PI3K/Akt/mTOR通路抑制内皮细胞过度自噬的直接证据，明确其关键调控节点，从FGF2-PI3K/Akt/mTOR通路抑制内皮细胞过度自噬的角度揭示USCs治疗DED的分子机制，为USCs治疗DED提供更充分的科学依据

The incidence of diabetic erectile dysfunction (DED) is getting higher, but the existing treatment is not effective. The core pathogenesis of DED is cavernous endothelial dysfunction. Our previous study verified that the excessive autophagy of cavernous endothelial cells (ECs) is an important mechanism of endothelial dysfunction of DED. Our previous study also demonstrated that transplantation of urine derived stem cells (USCs) could repair the endothelial function and erectile function in DED rats, the underlying mechanism is remained unknown. Our further study found that the fibroblast growth factor 2 (FGF2) secreted by USCs could inhibit the autophagy of ECs, which was associated with the activation of PI3K/Akt/mTOR pathway. Therefore, we hypothesis that USCs can activate the PI3K/Akt/mTOR pathway trough the paracrine of FGF2 to inhibit the excessive autophagy of ECs and thus repair the endothelial function and erectile function in DED rats. We intend to analyze the mechanism of FGF2 regulation of endothelial autophagy by cell co-culture, gene microarray, RPPA analysis and western blot et al. This program will obtain the direct evidence that FGF2 activates the PI3K/Akt/mTOR pathway to inhibit endothelial cell autophagy and repair the cavernous endothelial function and erection function, which will provide sufficient theoretical basis for the promotion of USCs as an effective treatment for diabetic erectile dysfunction.