Abstract
The aim of the present study was to explore the wound healing effect of Tcf3 in rat bone marrow mesenchymal stem cells (BMSCs) and their effects on wound healing. Epidermal growth factor (EGF) and fibroblast growth factors (FGFs) were used to induce BMSCs differentiation into epithelial-like cells. Western Blotting analysis and RT-qPCR were performed to assess the expression levels of Tcf3 and the markers of epithelial-like cells, such as Cytokeratin-18 (CK-18), CK-19 and P63. Cell counting kit-8 (CCK-8) and clone formation assay were carried out to detect cell viability. Immunohistochemistry and HE staining were used to assess the level of Tcf3 protein and skin repair degree, respectively. Rat wound healing model was built to evaluate the effects of BMSCs with altered expression of Tcf3 on wound healing. Results showed that EGF and FGFs stimulation increased the expression of CK-18, CK-19 and P63, improved BMSCs viability, but decreased the expression of Tcf3. Knockdown of Tcf3 in BMSCs increased CK-18, CK-19 and P63 expression and improved cell proliferation, as well as accelerated wound healing process. Moreover, inhibition of Wnt/β-catenin signaling weakened the effect of Tcf3 down-regulation on BMSCs proliferation enhancement. And inhibition of Notch1 signaling impeded the epithelial-like cell differentiation of BMSCs induced by Tcf3 down-regulation. Our study reveals that knockdown of Tcf3 enhances the wound healing process of BMSCs in rat, which provides new approach for accelerating skin regeneration.
Highlights
Wound healing progresses normally in the majority of population; it is compromised in several diseases, such as diabetes [1], chronic renal failure [2], and arterial or venous insufficiency [3,4]
We focused on the effects of Tcf3 on the epithelial-like cell transdifferentiation of bone marrow mesenchymal stem cell (BMSC), aiming to find potent method to enhance BMSCs function on wound healing
Our results revealed that knockdown of Tcf3 facilitated the epithelial-like cell transdifferentiation of BMSCs, which promoted the effects of BMSCs on accelerating wound healing process
Summary
Wound healing progresses normally in the majority of population; it is compromised in several diseases, such as diabetes [1], chronic renal failure [2], and arterial or venous insufficiency [3,4]. Marrow mesenchymal stem cells (SCs), referred as to stromal multipotent stromal cells, are self-renewing and expandable SCs. Bone marrow mesenchymal SCs (BMSCs) derived from bones are able to differentiate into adipocytes, osteoblasts, and chondrocytes [6]. Bone marrow mesenchymal SCs (BMSCs) derived from bones are able to differentiate into adipocytes, osteoblasts, and chondrocytes [6] Due to their properties of self-renewal and pluripotency, BMSCs are widely used for wound healing recently, and serve as the ideal seed cells for tissue engineering and regenerative medicine. Wu et al [7] revealed that BMSC-treated wounds exhibited significantly accelerated wound closure, with increased re-epithelialization, cellularity, and angiogenesis in normal mice and in diabetic mice, suggesting a direct contribution of BMSCs to cutaneous regeneration.
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