Department of Anesthesiology, Zhujiang Hospital of Southern Medical University, Guangzhou, China.
School of Medicine and Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
Contact Dermatitis. 2022 Apr;86(4):286-294. doi: 10.1111/cod.14051. Epub 2022 Feb 8.
Although the Mas-related G-protein-coupled receptors (Mrgprs) play essential roles in itch detection, their contribution to allergic contact dermatitis (ACD)-associated itch remains unclear.
To investigate whether Mrgprs are involved in ACD and whether Mrgprs can be identified as potential therapeutic targets.
Mrgpr-clusterΔ mice and human MrgprX1 (hMrgprX1) transgenic mice were used to evaluate the function of Mrgprs in oxazolone-induced ACD.
Utilizing an ACD model, we found that Mrgpr-clusterΔ mice display significantly reduced pruritus. Among 12 Mrgprs deleted in Mrgpr-clusterΔ mice, the expression of MrgprC11 and MrgprA3 was significantly increased in the ACD model, which also innervated the skin and spinal cord at higher-than-normal densities. The proportions of dorsal root ganglia neurons responding to bovine adrenal medulla peptide 8-22 and chloroquine were also remarkably increased in the ACD model, resulting in enhanced itch behaviour. To study the function of human Mrgprs in ACD-induced itch, we used hMrgprX1 transgenic mice, which rescued the severe itch defect of Mrgpr-clusterΔ mice in the ACD model. Remarkably, pharmacological blockade of hMrgprX1 significantly attenuates ACD itch in hMrgprX1 transgenic mouse.
Our study provides the first evidence that Mrgprs are involved in ACD-induced chronic itch, which provides new avenues for itch management in ACD.
虽然 Mas 相关 G 蛋白偶联受体（Mrgprs）在瘙痒检测中发挥着重要作用，但它们在过敏性接触性皮炎（ACD）相关瘙痒中的作用尚不清楚。
研究 Mrgprs 是否参与 ACD，以及 Mrgprs 是否可以被鉴定为潜在的治疗靶点。
使用 Mrgpr 簇Δ 小鼠和人 MrgprX1（hMrgprX1）转基因小鼠评估 Mrgprs 在噁唑酮诱导的 ACD 中的作用。
利用 ACD 模型，我们发现 Mrgpr 簇Δ 小鼠的瘙痒明显减轻。在 Mrgpr 簇Δ 小鼠中缺失的 12 种 Mrgprs 中，MrgprC11 和 MrgprA3 的表达在 ACD 模型中显著增加，并且在更高的密度下支配皮肤和脊髓。在 ACD 模型中，对牛肾上腺髓质肽 8-22 和氯喹有反应的背根神经节神经元的比例也显著增加，导致瘙痒行为增强。为了研究人 Mrgprs 在 ACD 诱导的瘙痒中的作用，我们使用了 hMrgprX1 转基因小鼠，该模型挽救了 Mrgpr 簇Δ 小鼠在 ACD 模型中的严重瘙痒缺陷。值得注意的是，hMrgprX1 的药理学阻断显著减轻了 hMrgprX1 转基因小鼠的 ACD 瘙痒。
本研究首次提供了证据表明 Mrgprs 参与 ACD 诱导的慢性瘙痒，为 ACD 瘙痒管理提供了新途径。
