Search

Background: The biological role of miR-203 and the underlying mechanisms on the proliferation of epidermal stem cells (ESCs) have not yet been reported during the progression of chronic wound healing in diabetes mellitus. Our previous studies have observed that the expression of miR-203 showed a marked upregulation and ESC proliferation capacity was impaired in diabetes mellitus skin wounds in rats. Methods: Wound models were established in normal rats and rats with type 2 diabetes. Expression level of miR-203 and the alteration of ESCs' number and function were detected. ESCs were isolated from the back skin of fetal rats to assess the effects of glucose in vitro. An antagomir to miR-203 was used to assess its effect on ESCs. Using microarray analysis, we further identified potential target genes and signaling pathways of miR-203. Results: We found that high glucose significantly upregulated the expression of miR-203 and subsequently reduced the number of ESCs and impaired their proliferation capacity. Meanwhile, over-expression of miR-203 reduced the ESCs' numbers and impaired the proliferation capacity via downregulation of the Notch and Wnt signaling pathways. Conversely, inhibition of miR-203 enhanced the proliferation capacity. Additionally, silencing miR-203 in skin of rats with type 2 diabetes accelerated wound healing and improved healing quality via the upregulation of the Notch and Wnt signaling pathways. Finally, over-expression of miR-203 downregulated genes ROCK2, MAPK8, MAPK9, and PRKCA. Conclusion: Our findings demonstrated that induced expression of miR-203 by high glucose in type 2 diabetic rats decreased the number of ESCs and impaired ESC proliferation capacity via downregulating genes related to Notch and Wnt signaling pathways, resulting in a delayed wound healing. [ABSTRACT FROM AUTHOR]

The skin has important barrier, sensory, and immune functions, contributing to the health and integrity of the organism. Extensive skin injuries that threaten the entire organism require immediate and effective treatment. Wound healing is a natural response, but in severe conditions, such as burns and diabetes, this process is insufficient to achieve effective treatment. Epidermal stem cells (EPSCs) are a multipotent cell type and are committed to the formation and differentiation of the functional epidermis. As the contributions of EPSCs in wound healing and tissue regeneration have been increasingly attracting the attention of researchers, a rising number of therapies based on EPSCs are currently under development. In this paper, we review the characteristics of EPSCs and the mechanisms underlying their functions during wound healing. Applications of EPSCs are also discussed to determine the potential and feasibility of using EPSCs clinically in wound healing. [ABSTRACT FROM AUTHOR]