同样，研究人员认为提高p53水平将可以促使更多的成纤维细胞转变为内皮细胞。由于p53往往在癌细胞中突变或丧失，已有大量的化合物被设计出来作为可能的抗癌治疗来提高它的水平。研究人员挑选了一种叫做RITA(Reactivation of p53 and Induction of Tumor cell Apoptosis，重新激活p53并诱导肿瘤细胞凋亡)的实验性药物，用它在心脏损伤后的数天里治疗小鼠。这一药物生成了引人注目的结果，它使得转变为内皮细胞的成纤维细胞数量增长至原来的两倍。这就是说，并非30%，而是有60%的成纤维细胞接通这一开关，自然转变为了内皮细胞。
Mesenchymal–endothelial transition contributes to cardiac neovascularization
Endothelial cells contribute to a subset of cardiac fibroblasts by undergoing endothelial-to-mesenchymal transition, but whether cardiac fibroblasts can adopt an endothelial cell fate and directly contribute to neovascularization after cardiac injury is not known. Here, using genetic fate map techniques, we demonstrate that cardiac fibroblasts rapidly adopt an endothelial-cell-like phenotype after acute ischaemic cardiac injury. Fibroblast-derived endothelial cells exhibit anatomical and functional characteristics of native endothelial cells. We show that the transcription factor p53 regulates such a switch in cardiac fibroblast fate. Loss of p53 in cardiac fibroblasts severely decreases the formation of fibroblast-derived endothelial cells, reduces post-infarct vascular density and worsens cardiac function. Conversely, stimulation of the p53 pathway in cardiac fibroblasts augments mesenchymal-to-endothelial transition, enhances vascularity and improves cardiac function. These observations demonstrate that mesenchymal-to-endothelial transition contributes to neovascularization of the injured heart and represents a potential therapeutic target for enhancing cardiac repair.
作者: 现代化研 时间: 2014-11-16 15:28
RITA(Reactivation of p53 and Induction of Tumor cell Apoptosis）软件译：RITA（p53基因的重新激活肿瘤细胞凋亡的诱导和）
