胶质疤痕形成是脊髓损伤重要的病理学特征，主要由活化的星形胶质细胞增殖引起，然而诱导胶质细胞活化和增殖机制尙不清楚。研究报道Hippo通路调节机体细胞增殖，我们预实验发现：①YAP特异性高表达于脊髓星形胶质细胞；②在划痕损伤细胞模型中，损伤区内星形胶质细胞核定位YAP显著降低， p-YAP增多；③沉默YAP后促进星形胶质细胞活化并抑制其增殖；④YAP表达量在脊髓损伤早期下调而在晚期显著上调。由此我们设想：脊髓损伤后是否通过激活YAP促进星形胶质细胞增殖，从而诱导胶质疤痕形成。本课题拟采用细胞生物学等技术进一步阐明YAP在星形胶质细胞激活和增殖中的作用及其分子机制。构建可诱导性、条件性YAP基因敲除小鼠，观察在脊髓损伤动物模型各个时期，YAP对胶质疤痕形成及对脊髓损伤再生修复的作用。本研究将首次深入阐述YAP信号通路在脊髓损伤胶质疤痕形成中的作用及分子机制，为今后的临床治疗提供新靶点和新思路。

Glial scarring after spinal cord injury(SCI) is mainly due to proliferation of reactive astrocytes, however, the underlying molecular mechanism of regulating the reactive gliosis response to injury remains unclear. The Hippo/YAP(Yes-Associated Protein) signaling pathway plays a key role in regulating cell proliferation, in addition, our preliminary data has shown that, ① YAP was specifically, highly expressed in astrocytes of spinal cord; ②In scratched injury model, nuclear YAP was dramatically decreased, whereas, cytoplasmic p-YAP was increased in injuried astrocytes; ③Knockdown YAP by RNAi promoted the activation but inhibited the proliferation of astocytes; ④YAP was dramatically decreased in early stage, and increased in late stage of spinal cord injury. Based on these preliminary data, we propose our hypothesis: during spinal cord injury, activation of astrocytic YAP promotes the proliferation of astrocytes, and leads to the formation of glial scars. To test this hypothesis, firstly, we will further examine the roles and mechanisms of YAP in astrocyte activation and proliferation by using cellular and molecular technologies. Secondly, we will exmamine the effects of astrocytic YAP in glial scars, and neural regeneration by using inducible and conditional YAP knockout mice with spinal cord injuried model. This study will help to understand the roles and mechanisms of Hippo/YAP pathways in glia scar formation after spinal cord injury, and provide new targets and new insights for spinal cord injury therapies.