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Diabetes and Cannabinoid CB1 receptor deficiency promotes similar early onset aging-like changes in the skin
Experimental Gerontology ( IF 3.3 ) Pub Date : 2021-08-24 , DOI: 10.1016/j.exger.2021.111528
Ermelindo C Leal 1 , Liane I F Moura 2 , Roksana M Pirzgalska 2 , Dorinda Marques-da-Silva 2 , Catherine Ledent 3 , Attila Köfalvi 2 , Eugenia Carvalho 4
Affiliation  

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。

更新日期:2021-08-26
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