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尿囊素通过激活慢性肾脏病中的 MrgprD 引起瘙痒。

Allantoin induces pruritus by activating MrgprD in chronic kidney disease.

机构信息

School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.

Department of Pharmacy, General Hospital of Eastern Theater Command, Nanjing, China.

出版信息

J Cell Physiol. 2023 Apr;238(4):813-828. doi: 10.1002/jcp.30977. Epub 2023 Mar 6.

DOI:10.1002/jcp.30977
PMID:36879552
Abstract

Chronic kidney disease (CKD) is a disease with decreased, irreversible renal function. Pruritus is the most common skin symptom in patients with CKD, especially in end-stage renal disease. The underlying molecular and neural mechanism of CKD-associated pruritus (CKD-aP) remains obscure. Our data show that the level of allantoin increases in the serum of CKD-aP and CKD model mice. Allantoin could induce scratching behavior in mice and active DRG neurons. The calcium influx and action potential reduced significantly in DRG neurons of MrgprD KO or TRPV1 KO mice. U73122, an antagonist of phospholipase C, could also block calcium influx in DRG neurons induced by allantoin. Thus, our results concluded that allantoin plays an important role in CKD-aP, mediated by MrgprD and TrpV1, in CKD patients.

摘要

慢性肾脏病(CKD)是一种肾功能下降且不可逆转的疾病。瘙痒是 CKD 患者最常见的皮肤症状,尤其是在终末期肾病患者中。CKD 相关瘙痒(CKD-aP)的潜在分子和神经机制仍不清楚。我们的数据表明,CKD-aP 和 CKD 模型小鼠的血清中尿囊素水平升高。尿囊素可诱导小鼠搔抓行为和活性 DRG 神经元。在 MrgprD KO 或 TRPV1 KO 小鼠的 DRG 神经元中,钙内流和动作电位显著减少。PLC 的拮抗剂 U73122 也可阻断尿囊素诱导的 DRG 神经元内的钙内流。因此,我们的研究结果表明,在 CKD 患者中,尿囊素通过 MrgprD 和 TrpV1 介导,在 CKD-aP 中发挥重要作用。

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