Purpose: Type 2 diabetes mellitus (DM) induces various dermatological conditions that can affect patient quality of life, including increased susceptibility to skin infections and dry skin. While the mechanisms that underlie the causes of dry skin in type 1 DM have been widely studied, how type 2 DM elicits similar effects is unclear. The purpose of this study was therefore to evaluate skin barrier and hydration function using a KK-A^y/TaJcl mouse model of type 2 DM. Materials and methods: KK-A^y/TaJcl and control mice were housed separately for 4 weeks and then body weight, water intake, urine production, and blood glucose levels were measured. Skin barrier function was estimated by assessing transepidermal water loss (TEWL) and hydration levels of the stratum corneum. The expression levels of various skin biochemical factors were also examined by western blot, including type 1 collagen, mast cell tryptase, hyaluronic acid binding protein (HABP), and fibroblast protein S100A4. Results: Compared to control mice, there was a marked increase in body weight, water intake, urine production, and blood glucose levels in the KK-A^y/TaJcl mice over the length of the experiment. Hydration levels in the stratum corneum were lower in KK-A^y/TaJcl mice compared to control mice, although TEWL was not significantly different between groups. We also found that hyaluronic acid binding protein expression was higher in KK-A^y/TaJcl mice, although other biochemical factors were the same. Conclusions: These findings suggest that hyaluronic acid associates with the dry skin caused by type 2 DM. This contributes to understanding this phenomenon and may lead to better treatment options for patients in the future.

Type 2 diabetes is a lifestyle-related disease that affects people worldwide and is especially prevalent in the elderly. Many elderly people with diabetes also complain of dry skin; however, the relationship between aging and dry skin in type 2 diabetes is unknown. The purpose of this study was to examine the interaction between aging and dry skin using the specific pathogen-free KK-Ay/TaJcl type 2 diabetes mouse model. Skin dryness in this model increases with age and was evaluated at 10, 27, 40, and 50 weeks. We observed increased mast cell expression, increased histamine and matrix metalloproteinase-1 levels, and decreased collagen expression in the skin of aging KK-Ay/TaJcl mice. In addition, the increased expression of angiopoietin 2, interleukin-6, tumor necrosis factor-α, and endostatin in the blood indicated kidney damage in this model. Aging KK-Ay/TaJcl mice also showed fatty liver pathology, which led to increased reactive oxygen species in the blood and liver, as well as the increased expression of M1 macrophages in the liver. These results showed that dry skin is associated with skin, kidney, and liver interactions in an aging type 2 diabetes mouse model.

Background: Dry skin induced by rheumatoid arthritis (RA) causes itching, which negatively influences a patient’s quality of life. We previously reported that mast cells are related to dry skin in arthritic mice. However, the mechanism of mast cell activation is unclear. In this study, we examined the mechanism underlying the formation of dry skin induced by mast cells in arthritis that involves thymic stromal lymphopoietin (TSLP), neutrophils, reactive oxygen species (ROS), and glucocorticoids. Methods: Mice with DBA/1JJmsSlc collagen-induced arthritis were treated with inhibitors or neutralizing antibodies. We measured transepidermal water loss (TEWL) to examine the modulating signal of mast cells. Results: TEWL, the number of mast cells, and the plasma levels of TSLP, ROS, and corticosterone in the arthritic mice were increased when compared with the control mice. However, the mice treated with TSLP- and neutrophil-neutralizing antibodies and ROS and glucocorticoid receptor inhibitors (N-acetyl-L-cysteine [NAC] and RU-486, respectively) experienced an improvement. The ameliorating effect was most remarkable following treatment with NAC + RU-486. Conclusion: This study suggested that inhibiting ROS and glucocorticoids is important to ameliorate dry skin in arthritis, which may provide a novel treatment option for dry skin in RA patients.

Purpose: Rheumatoid arthritis (RA) is known to induce dry skin as an extra-articular symptom. However, the mechanisms behind the induction are unclear. In this study, we utilized an arthritis mouse model to simulate RA to reveal the relationship between arthritis and dry skin. Materials and methods: DBA/1JJmsSlc control mice (n = 5) and DBA/1JJmsSlc collagen-induced arthritis mouse model (arthritis mice; n = 5) were used. We measured transepidermal water loss (TEWL) and capacitance to reveal the effect of arthritis on skin barrier function. In addition, we measured the expression of biomarkers of skin barrier function. Results: We found that the hind limb volume of the arthritis mice was higher than that of the control mice. Our results showed that the arthritis mice had higher TEWL and lower capacitance when compared to the control mice. When compared to that of the control mice, the skin of the arthritis mice was thicker with more leukocyte infiltration. In the skin of arthritis mice, we observed lower expression of type I and IV collagens, but higher expression of matrix metalloproteinases (MMP)-1 and -9 when compared to that of the control mice. The levels of mast cells, histamine, substance P, and tryptase were higher in the arthritis mice than in the control mice. This study showed that the arthritis mice exhibited a disruption of skin barrier function (i.e. dry skin), which was improved following treatment with a mast cell inhibitor. Conclusions: Our results on mast cells suggested that an improvement of dry skin is important for RA management.

Background: Vitamin C plays a part in various roles in the human body. In this study, we examined the effect of oral administration of high-dose vitamin C on the skin dryness induced by irinotecan. Methods: To establish the experimental model of irinotecan-induced skin dryness, the drug was intraperitoneally administered for four consecutive days. Simultaneously, oral administration of high-dose vitamin C (4 g/kg) was continued for 4 days. Results: High-dose vitamin C administration ameliorated the skin dryness induced by irinotecan. The expression of caspase-3 and caspase-9, reactive oxygen species, and the number of TUNEL-positive cells increased in the skin of irinotecan-treated mice but were lowered by high-dose vitamin C administration. In contrast, fibroblasts and collagen type I decreased in the skin of the irinotecan-treated mice but was increased by high-dose vitamin C administration. Conclusion: These results suggested that high-dose vitamin C administration can improve the skin dryness induced by irinotecan.