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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.
Mice that were knocked out of the response to centrifugal force and shear stress gene 1 (RECS1) were predisposed to cystic neovascular necrosis and arterial dilatation accompanied by an increase in the expression of matrix metalloproteinase 9 Previous study found that RECS1 stably expressing mouse fibroblasts on tumor necrosis factor 2 receptor agonist antibody was significantly weakened, indicating that RECS1 involved in the regulation of tumor necrosis factor signal.In this study, RECS1 on tumor necrosis factor receptor RECR1, TNFR1, and TNFR1, and RECS1 binds to TNFR1 and inhibits NF-κB activation induced by overexpression of TNFR1.Researches found that mutations in RECS1 Both NPLY and SPEDY motifs are necessary for their inhibition of TNFR1 signaling.Induced by immunoprecipitation that NPLY is required for the binding of RECS1 to TNFR1, the absence of SPEDY does not affect the binding of RECS1 to TNFR 1. In addition, co-immunoprecipitation Experiments show that RECS1 and TNFR1 co-localized in the nucleus of the nucleus.These results further reveal RECS1 negative regulation of tumor necrosis factor-α (tumor necrosis facto r-α, TNF-α) signal and then participate in the regulation of vascular development and remodeling of biological function and possible mechanism.