DKK3 (Dikkopf-3) Transdifferentiates Fibroblasts Into Functional Endothelial Cells—Brief Report

• DOI: 10.1161/atvbaha.118.311919
• Publication Date: 2019-02-28T14:40:00Z
• Authors: Ting Chen; Eirini Karamariti; Xuechong Hong; Jiacheng Deng; Yutao Wu; Wenduo Gu; Russell Simpson; Mei Mei Wong; Baoqi Yu; Yanhua Hu; Aijuan Qu; Qingbo Xu; Li Zhang
• Keywords: STAT3 Transcription Factor; 0301 basic medicine; 570; Epithelial-Mesenchymal Transition; endothelium; 610; Neovascularization, Physiologic; fibroblast; Mice; 03 medical and health sciences; Bioreactors; Mice, Inbred NOD; Animals; Humans; human; Cells, Cultured; Adaptor Proteins, Signal Transducing; Endothelial Cells; Fibroblasts; Vascular Endothelial Growth Factor Receptor-2; Recombinant Proteins; Culture Media; MicroRNAs; regeneration; Cell Transdifferentiation; endothelial cell

Objective— To determine the role of a cytokine-like protein DKK3 (dikkopf-3) in directly transdifferentiating fibroblasts into endothelial cells (ECs) and underlying mechanisms. Approach Results— overexpression human under defined conditions for 4 days led to notable change cell morphology progenitor gene expression. It was revealed that these went through mesenchymal-to-epithelial transition subsequently expressed KDR (kinase insert domain receptor) at high levels. Further culture EC media differentiation progenitors functional ECs capable angiogenesis both vitro vivo, which regulated by VEGF (vascular growth factor)/miR (microRNA)-125a-5p/Stat3 (signal transducer activator transcription factor 3) axis. More importantly, fibroblast-derived showed ability form patent endothelium-like monolayer tissue-engineered vascular grafts ex vivo. Conclusions— These data demonstrate is differentiating provides novel potential strategy regeneration.