离心力和剪应力应答蛋白1是肿瘤坏死因子受体1的新调控因子

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.

Responsive to Centrifugal Force and Shear Stress Gene 1 Encodes a Regulatory Protein of Tumor Necrosis Factor Receptor 1

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.