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DKK3 (Dikkopf-3) Transdifferentiates Fibroblasts Into Functional Endothelial Cells-Brief Report
Ting Chen1, Eirini Karamariti2, Xuechong Hong2
1From the Department of Cardiology, the First Affiliated Hospital, School of Medicine, Zhejiang University, China (T.C., Y.W., Q.X., L.Z.).
Arteriosclerosis, Thrombosis, and Vascular Biology
|March 1, 2019
Summary
Dickkopf-3 (DKK3) protein directly transforms human fibroblasts into functional endothelial cells (ECs). This discovery offers a new strategy for endothelial regeneration and tissue engineering applications.
Area of Science:
- Cell Biology
- Regenerative Medicine
- Molecular Biology
Background:
- Fibroblast transdifferentiation into endothelial cells (ECs) is crucial for vascular regeneration.
- Identifying novel factors that promote direct fibroblast-to-EC differentiation is a key research area.
Purpose of the Study:
- To investigate the role of Dickkopf-3 (DKK3) in directly transdifferentiating human fibroblasts into functional ECs.
- To elucidate the molecular mechanisms underlying DKK3-induced endothelial cell generation.
Main Methods:
- Overexpression of DKK3 in human fibroblasts under defined culture conditions.
- Analysis of cell morphology, gene expression (including KDR), and mesenchymal-to-epithelial transition markers.
- Assessment of differentiated cell function (angiogenesis in vitro/in vivo) and regulation by the VEGF/miR-125a-5p/Stat3 axis.
- Evaluation of fibroblast-derived ECs in tissue-engineered vascular grafts.
Main Results:
- DKK3 overexpression induced significant morphological changes and progenitor gene expression in fibroblasts.
- Cells underwent mesenchymal-to-epithelial transition and highly expressed KDR.
- Differentiated cells formed functional ECs capable of angiogenesis, regulated by the VEGF/miR-125a-5p/Stat3 pathway.
- Fibroblast-derived ECs formed a patent endothelium-like monolayer in vascular grafts.
Conclusions:
- DKK3 directly differentiates human fibroblasts into functional ECs under defined conditions.
- This process is mechanistically linked to the VEGF/miR-125a-5p/Stat3 signaling axis.
- DKK3 represents a novel therapeutic strategy for endothelial regeneration and vascular tissue engineering.
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