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Papers of the Week

Papers: 1 Feb 2020 - 7 Feb 2020

Animal Studies


2020 08

J Invest Dermatol



PAR2 mediates itch via TRPV3 signaling in keratinocytes.


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
J Invest Dermatol. 2020 08; 140(8):1524-1532.
PMID: 32004565.


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.