Background

The cannabinoid receptor type-1 (CB₁R) is a major regulator of metabolism, growth and inflammation. Yet, its potential role in the skin is not well understood. Our aim was to evaluate the role of CB₁R in aging-like diabetic skin changes by using a CB₁R knockout mouse model.

Methods

We evaluated several signals of skin aging in wild-type control (WT), WT streptozotocin-induced type 1 diabetic mice (WT DM), CB₁R knockout (CB₁RKO) and CB₁RKO DM mice. We quantified markers of inflammation, angiogenesis, antioxidant enzymes and collagen content. Moreover, we evaluate reactive oxygen species (ROS) levels and macrophage phenotype, M1 and M2.

Results

CB₁R expression is decreased in the skin of WT DM mice and collagen levels are decreased in the skin of WT DM, CB₁RKO and CB₁RKO DM mice. Additionally, the absence of CB₁R correlated with higher expression of pro-inflammatory markers, also evident in WT DM or CB₁RKO DM mice. Moreover, the M1/M2 macrophage ratio and ROS levels were significantly elevated but in the diabetic WT and the CB₁RKO mice, consistent with a significant decrease in the antioxidant capacity of the skin.

Conclusions

Our results indicate that CB₁R deficiency in the skin may lead to accelerated skin aging due to the increased production of ROS, a decrease in the antioxidant defenses and a higher pro-inflammatory environment. A significant decrease in the CB₁R expression may be a significant contributing factor to the early aging-like changes in diabetes.

中文翻译：

---

糖尿病和大麻素 CB1 受体缺乏会促进皮肤出现类似的早发性衰老样变化

背景

大麻素受体 1 型 (CB ₁ R) 是代谢、生长和炎症的主要调节剂。然而，它在皮肤中的潜在作用尚不清楚。_{我们的目的是通过使用 CB 1} R 基因敲除小鼠模型来评估 CB ₁ R 在老化样糖尿病皮肤变化中的作用。

方法

我们评估了野生型对照 (WT)、WT 链脲佐菌素诱导的 1 型糖尿病小鼠 (WT DM)、CB ₁ R 敲除 (CB ₁ RKO) 和 CB ₁ RKO DM 小鼠的皮肤衰老信号。我们量化了炎症、血管生成、抗氧化酶和胶原蛋白含量的标志物。此外，我们评估活性氧 (ROS) 水平和巨噬细胞表型 M1 和 M2。

结果

WT DM 小鼠皮肤中CB ₁ R 表达降低，WT DM、CB ₁ RKO 和CB ₁ RKO DM 小鼠皮肤中胶原蛋白水平降低。此外，CB ₁ R 的缺失与促炎标志物的更高表达相关，这在 WT DM 或 CB ₁ RKO DM 小鼠中也很明显。此外，M1/M2 巨噬细胞比率和 ROS 水平显着升高，但在糖尿病 WT 和 CB ₁ RKO 小鼠中，与皮肤抗氧化能力显着降低一致。

结论

我们的研究结果表明，由于 ROS 的产生增加、抗氧化防御能力下降和促炎环境升高，皮肤中 CB ₁ R 缺乏可能导致皮肤加速老化。CB ₁ R 表达的显着降低可能是糖尿病早期衰老样变化的重要促成因素。