Abstract While the effect of hyperglycemia on cutaneous wound healing is well recognized, the impact of high-glucose (HG) environment on UVB-induced skin tumor formation remains inconclusive. Similar to impaired wound healing, skin tumor formation involves keratinocyte proliferation and migration. Intriguingly, SOX2 has been recognized to play an important role in both wound healing and UVB-induced skin tumor formation by modulating cell proliferation and migration. As hyperglycemia results in impaired cutaneous wound healing, we hypothesized that the HG environment also impacts UVB-induced tumor formation of the skin. The present study aimed to explore the effects of HG environment on epidermal keratinocytes, focusing on the impact of UVB-induced cell proliferation and migration via SOX2 expression. In cultured keratinocytes, HG-cultivated keratinocytes showed reduced SOX2 levels compared to control with or without UVB treatment. SOX2 regulates keratinocyte migration and proliferation via modulation of AKT phosphorylation. Additionally, O-linked-N-acetylglucosamine glycosylation contributed to reduced SOX2 levels in HG-cultivated keratinocytes. Animal studies demonstrated that diabetic mice skin has significantly less UVB-induced tumor formation, epidermal thickening, SOX2, and pAKT expression than the control mice; mutant p53 expression was also lower in diabetic mice but did not reach statistical significance compared to control. In conclusion, HG environment reduces UVB-induced keratinocyte proliferation and migration, in association with decreased SOX2 expression and downstream AKT signaling. The current findings provide novel insights regarding UVB-induced skin tumor formation of skin in patients with diabetes.
Yang et al. (Fri,) studied this question.
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