2020.02.06 Journal Club

PAR2 mediates itch via TRPV3 signaling in keratinocytes

Jiahui Zhao, Admire Munanairi, Xian-Yu Liu, Jie Zhang, Linghan Hu, Meiqin Hu, Dingfang Bu, Lingling Liu, Zhiqiang Xie, Brian S. Kim, Yong Yang, Zhou-Feng Chen

The Journal of Investigative Dermatology

20 August 2019
10 December 2019 12 January 2020

Please cite this article as: Zhao J, Munanairi A, Liu X-Y, Zhang J, Hu L, Hu M, Bu D, Liu L, Xie Z,
Kim BS, Yang Y, Chen Z-F, PAR2 mediates itch via TRPV3 signaling in keratinocytes, The Journal of Investigative Dermatology (2020), doi: https://doi.org/10.1016/j.jid.2020.01.012.

Abstract

Animal studies have suggested that transient receptor potential (TRP) ion channels and G protein-coupled receptors (GPCRs) play important roles in itch transmission. TRPV3 gain-of-function mutations have been identified in patients with Olmsted syndrome which is associated with severe pruritus. However, the mechanisms causing itch remain poorly understood. Here, we show that keratinocytes lacking TRPV3 impair the function of protease activated receptor 2 (PAR2), resulting in reduced neuronal activation and scratching behavior in response to PAR2 agonists. Moreover, we show that TRPV3 and PAR2 were upregulated in skin biopsies from patients and mice with atopic dermatitis (AD), whereas their inhibition attenuated scratching and inflammatory responses in mouse AD models. Taken together, these results reveal a previously unrecognized link between TRPV3 and PAR2 in keratinocytes to convey itch information and suggest that a blockade of PAR2 or TRPV3 individually or both may serve as a potential approach for antipruritic therapy in AD.

Key Words

TRPV3PAR2itchkeratinocytescalciumatopic dermatitis

Abbreviations

ADatopic dermatitisBAM 8-22bovine adrenal medulla peptide 8-22DRGdorsal root gangliaGPCRG protein coupled receptorMrgprMas-related G-protein coupled receptorPAR2protease-activated receptor 2TRPV3transient receptor potential cation channel V3TSLPthymic stromal lymphopoietin