DKK3 (Dikkopf-3) Transdifferentiates Fibroblasts Into Functional Endothelial Cells-Brief Report
DKK3 (Dikkopf-3) Transdifferentiates Fibroblasts Into Functional Endothelial Cells-Brief Report
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DKK3 (Dikkopf-3) 将成纤维细胞转分化为功能性内皮细胞 - 简要报告
DOI：
10.1161/atvbaha.118.311919
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发表时间：
2019-04-01
影响因子：
8.7
通讯作者：
Zhang, Li
中科院分区：
文献类型：
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作者：
Chen, Ting;Karamariti, Eirini;Zhang, Li
目的 - 确定细胞因子样蛋白DKK3（Dikkopf-3）在直接转分化成纤维细胞中的作用，并将其作用。方法和结果-DKK3在定义条件下人类成纤维细胞中的过表达4天导致细胞形态和祖细胞基因表达的显着变化。据显示，这些细胞经过间充质到上皮过渡，随后在高水平的高水平表达KDR（激酶插入域受体）。在EC定义的培养基中的进一步培养导致这些祖细胞分化为能够在体外和体内进行血管生成的功能性EC，该功能受到VEGF（血管内皮生长因子）/miR（microRNA）-125A-5P/STAT3（信号）（信号）转录因子3）轴的换能器和激活因子。更重要的是，成纤维细胞衍生的EC表现出在组织工程的血管移植物中形成专利内皮样单层的能力。结论 - 这些数据表明，DKK3能够将人类成纤维细胞与定义培养基下的功能性EC直接区分开，并为内皮再生提供了新的潜在策略。
Objective- To determine the role of a cytokine-like protein DKK3 (dikkopf-3) in directly transdifferentiating fibroblasts into endothelial cells (ECs) and the underlying mechanisms. Approach and Results- DKK3 overexpression in human fibroblasts under defined conditions for 4 days led to a notable change in cell morphology and progenitor gene expression. It was revealed that these cells went through mesenchymal-to-epithelial transition and subsequently expressed KDR (kinase insert domain receptor) at high levels. Further culture in EC defined media led to differentiation of these progenitors into functional ECs capable of angiogenesis both in vitro and in vivo, which was regulated by the VEGF (vascular endothelial growth factor)/miR (microRNA)-125a-5p/Stat3 (signal transducer and activator of transcription factor 3) axis. More importantly, fibroblast-derived ECs showed the ability to form a patent endothelium-like monolayer in tissue-engineered vascular grafts ex vivo. Conclusions- These data demonstrate that DKK3 is capable of directly differentiating human fibroblasts to functional ECs under defined media and provides a novel potential strategy for endothelial regeneration.