Xeroderma is a frequent complication in diabetic patients. In this study, we investigated the mechanism underlying the onset of diabetic xeroderma, focusing on aquaporin-3 (AQP3), which plays an important role in water transport in the skin. Dermal water content in diabetic mice was significantly lower than that in control mice. The expression level of AQP3 in the skin was significantly lower in diabetic mice than in control mice. One week after streptozotocin (STZ) treatment, despite their increased blood glucose levels, mice showed no changes in the expression levels of AQP3, Bmal1, Clock, and D site-binding protein (Dbp) in the skin and 8-hydroxydeoxyguanosine (8-OHdG) in the urine. In contrast, two weeks after STZ treatment, mice showed increases in the blood glucose level, decreases in AQP3, Bmal1, Clock, and Dbp levels, and increases in the urinary levels of 8-OHdG. The results of this study suggest that skin AQP3 expression decreases in diabetes, which may limit water transport from the vessel side to the corneum side, causing dry skin. In addition, in diabetic mice, increased oxidative stress triggered decreases in the expression levels of Bmal1 and Clock in the skin, thereby inhibiting the transcription of Aqp3 by Dbp, which resulted in decreased AQP3 expression.

Xeroderma is induced by diabetes, reducing patients’ quality of life. We aimed to clarify the roles of cutaneous water channel aquaporin-3 (AQP3) in diabetic xeroderma using type 2 diabetes model db/db mice. Blood glucose levels were unchanged in 5-week-old db/db mice compared to db/+ mice (control mice), but the pathophysiology of type 2 diabetes was confirmed in 12-week-old db/db mice. The dermal water content and AQP3 expression in 5-week-old db/db mice were almost the same as those in the control mice. On the other hand, in 12-week-old db/db mice, the dermal water content and AQP3 expression were significantly decreased. The addition of glucose to HaCaT cells had no effect on AQP3, but tumor necrosis factor-α (TNF-α) decreased the AQP3 expression level. Blood TNF-α levels or skin inflammation markers in the 12-week-old db/db mice were significantly higher than those in control mice. AQP3 levels in the skin were decreased in type 2 diabetes, and this decrease in AQP3 may be one of the causes of xeroderma. Therefore, a substance that increases AQP3 may be useful for improving xeroderma. Additionally, a decrease in skin AQP3 may be triggered by inflammation. Therefore, anti-inflammatory drugs may be effective as new therapeutic agents for diabetic xerosis.

Sasa veitchii (S. veitchii) is a traditional herb derived from the bamboo genus, which is collectively called Kumazasa. Although Kumazasa extract is believed to have various effects on the skin, there is little scientific evidence for these effects. In this study, we aimed to obtain scientific evidence regarding the wound-healing and skin-moisturizing effects of Kumazasa extract. Kumazasa extract was applied to the skin of a mouse wound model for 14 days, and the wound area and dermal water content were measured. Mice treated with Kumazasa extract had smaller wound areas than control mice. The dermal water content in the Kumazasa extract-treated group was significantly higher than that in the control group. The mRNA and protein expression levels of cutaneous aquaporin-3 (AQP3), which is involved in wound healing and increases in dermal water content, were significantly increased by treatment with Kumazasa extract. Kumazasa extract-treated HaCaT cells exhibited significantly higher AQP3 expression and p38 mitogen-activated protein kinase (MAPK) phosphorylation than control cells. With continuous application, Kumazasa extract increases AQP3 expression and exerts wound-healing and moisturizing effects. The increase in AQP3 expression elicited by Kumazasa extract may be due to enhancement of transcription via activation of p38 MAPK signaling.