microRNA-203 Modulates Wound Healing and Scar Formation via Suppressing Hes1 Expression in Epidermal Stem Cells

Abstract

Background/Aims: Little is known how miR-203 is involved in epidermal stem cells (ESCs) differentiation and scar formation. Methods: We first used luciferase assay to determine the interaction of miR-203 with the 3’-UTR in regulation of Hes1 expression. We then used flow cytometry to analyze the effects of miR-203 expression on the differentiation of ESCs to MFB by determination of CK15 ratio and α-SMA. To confirm the results of flow cytometry analysis, we used Western blot to examine the expression of α-SMA, Collagen I (Col I), and Collagen III (Col III), as well as the expression of Notch1, Jagged1, and Hes1 in ESCs after the treatment of pre-miR-203 or anti-miR-203. Finally, we examined the effects local anti-miR-203 treatment on would closure and scar formation using a mouse skin wound model. Results: Pre-miR-203 treatment increased ESCs differentiation to MFB cells, as indicated by decreased CK15 ratio and increased MFB biomarkers. This phenomenon was reversed by overexpression of Hes1 in ESCs. In addition, skin incision increased expression of miR-203 in wound tissue. Local treatment of anti-miR-203 could accelerate wound closure and reduce scar formation in vivo, which was associated with increased re-epithelialization, skin attachment regeneration, and collagen reassignment. Finally, we confirmed that anti-miR-203 treatment could inhibit ESCs differentiation in vivo via increasing Hesl expression. Conclusion: Taken together, our results suggested that overexpression of miR-203 in ESCs after skin wound may be a critical mechanism underlying the scar formation.

Epidermal Stem Cells in Wound Healing and Regeneration

“…However, the low specific expression of Hes1 leads to a limited proliferation of skin EpiSCs, impeding the epithelialization process. Thus, skin barrier function damage and abnormal hair development occur [79,80]. One of the explanations is that the Notch signaling pathway can regulate stem cell adhesion; the latter affects the biological microenvironment ("niche") of stem cells.…”

Association between histopathological changes and expression of selected microRNAs in skin of adult patients with IgA vasculitis

“…miR-203 shows the highest expression level in the skin, as compared with other organs, and plays an important role in skin-healing processes. 30 Our results therefore suggest that miR-203-3p might also be involved in these processes in IgAV. In addition, the altered expression of miR-203 found in psoriasis 31 and rheumatoid arthritis 32 suggests its involvement in immune-mediated diseases.…”

“…We noticed that mild granulocyte infiltration, without signs of fibrinoid necrosis, was mostly present in clinically older or healing skin lesions. miR‐203 shows the highest expression level in the skin, as compared with other organs, and plays an important role in skin‐healing processes . Our results therefore suggest that miR‐203‐3p might also be involved in these processes in IgAV.…”

Assessment of transcriptional activity genes associated with the IL‐17 signaling pathway in skin fibroblasts under the influence of adalimumab

“…A decrease in its expression at the level of transcriptome and proteome after TNF inhibitor therapy has been confirmed (Skarmoutsou et al, ). Zhou et al ()) describe the key role of the HES1 gene in promoting stem cell proliferation and inhibiting their differentiation, which is important when rebuilding the skin barrier, scarring after injury, and injury. In this study, an increase in HES1 expression can be observed, which indicates that proliferation processes are induced under the influence of adalimumab.…”