中文摘要：

离心力和剪应力应答基因1（responsive to centrifugal force and shear stress gene 1,RECS1）被剔除的小鼠易患囊性内侧坏死和动脉扩张症,伴随着血管组织基质金属蛋白酶9表达水平的增强.本室前期研究发现,稳定表达RECS1的小鼠成纤维细胞对肿瘤坏死因子受体2激动性抗体的敏感性被明显弱化,显示RECS1参与肿瘤坏死因子信号的调控.本文研究了RECS1对肿瘤坏死因子受体1（tumor necrosis factor receptor-1,TNFR1）的调控作用.结果显示,RECS1结合TNFR1,并抑制过量表达TNFR1诱导的核转录因子-κB（NF-κB）活化.缺失突变研究发现,RECS1分子上有NPLY和SPEDY两个模体是其抑制TNFR1信号所必需的.免疫共沉淀实验发现,NPLY是RECS1与TNFR1结合所必需的.而SPEDY的缺失不影响RECS1与TNFR1的结合.另外,免疫共染色实验显示,RECS1与TNFR1共定位于细胞内核体.这些实验结果进一步揭示了RECS1负调控肿瘤坏死因子-α（tumor necrosis factor-α,TNF-α）信号进而参与调控血管发育与重塑的生物功能及可能机理.

英文摘要：

Responsive to centrifugal force and shear stress gene 1（Recs1） was reported to be involved in the regulation of tumor necrosis factor-α（TNF-α） signaling.RECS1 knockout mice were prone to cystic medium degeneration and aortic dilation,accompanied by enhanced expression of matrix metalloproteinase 9.We identified RECS1 as an interacting protein of tumor necrosis factor receptor 1（TNFR1） and negatively regulated TNFR1-induced NF-κB activation.Two motifs NPLY and SPEDY were characterized and shown to be essential for the inhibitory effect of RECS1 on TNFR1-mediated NF-κB activation,although the deletion of SPEDY did not affect the interaction of RECS1 with TNFR1.In addition,immunostaining showed a partial endosomal colocalization of RECS1 with TNFR1.The participation of RECS1 in the regulation of vascular development and remodeling by negatively regulating TNF-α signaling needs to be further demonstrated.