Study of the Mechanism Underlying the Onset of Diabetic Xeroderma Focusing on an Aquaporin-3 in a Streptozotocin-Induced Diabetic Mouse Model
Study of the Mechanism Underlying the Onset of Diabetic Xeroderma Focusing on an Aquaporin-3 in a Streptozotocin-Induced Diabetic Mouse Model
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DOI：
10.3390/ijms20153782
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发表时间：
2019-08-01
影响因子：
5.6
通讯作者：
Kamei, Junzo
中科院分区：
文献类型：
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作者：
Ikarashi, Nobutomo;Mizukami, Nanaho;Kamei, Junzo
干皮病是糖尿病患者常见的并发症。在这项研究中，我们研究了糖尿病性干皮病发病的机制，重点关注水通道蛋白-3 (AQP3)，它在皮肤中的水分运输中发挥着重要作用。糖尿病小鼠的真皮含水量显着低于对照小鼠。糖尿病小鼠皮肤中 AQP3 的表达水平显着低于对照小鼠。链脲佐菌素 (STZ) 治疗一周后，尽管小鼠血糖水平升高，但皮肤中 AQP3、Bmal1、Clock 和 D 位点结合蛋白 (Dbp) 以及尿液中 8-羟基脱氧鸟苷 (8-OHdG) 的表达水平没有变化。相比之下，STZ 治疗两周后，小鼠血糖水平升高，AQP3、Bmal1、Clock 和 Dbp 水平降低，尿 8-OHdG 水平升高。这项研究的结果表明，糖尿病患者皮肤AQP3表达降低，这可能会限制水分从血管侧输送到角质层侧，导致皮肤干燥。此外，在糖尿病小鼠中，氧化应激增加引发皮肤中Bmal1和Clock表达水平下降，从而抑制Dbp对Aqp3的转录，从而导致AQP3表达下降。
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.