2. Academic Validation
  3. PAR2 Mediates Itch via TRPV3 Signaling in Keratinocytes

PAR2 Mediates Itch via TRPV3 Signaling in Keratinocytes

  • J Invest Dermatol. 2020 Aug;140(8):1524-1532. doi: 10.1016/j.jid.2020.01.012.
Jiahui Zhao 1,  Admire Munanairi 2,  Xian-Yu Liu 3,  Jie Zhang 4,  Linghan Hu 5,  Meiqin Hu 6,  Dingfang Bu 4,  Lingling Liu 4,  Zhiqiang Xie 7,  Brian S Kim 8,  Yong Yang 9,  Zhou-Feng Chen 10
Affiliations

Affiliations

  • 1 Department of Dermatology, Peking University First Hospital, Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, National Clinical Research Center for Skin and Immune Disease, Beijing, China; Center for the Study of Itch and Sensory Disorders, Washington University School of Medicine, St. Louis, USA.
  • 2 Center for the Study of Itch and Sensory Disorders, Washington University School of Medicine, St. Louis, USA; Department of Anesthesiology, Washington University School of Medicine, St. Louis, USA; Current Address: Department of Pediatrics, Washington University School of Medicine, St. Louis, USA.
  • 3 Center for the Study of Itch and Sensory Disorders, Washington University School of Medicine, St. Louis, USA; Department of Anesthesiology, Washington University School of Medicine, St. Louis, USA.
  • 4 Department of Dermatology, Peking University First Hospital, Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, National Clinical Research Center for Skin and Immune Disease, Beijing, China.
  • 5 Department of Dermatology, Peking University First Hospital, Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, National Clinical Research Center for Skin and Immune Disease, Beijing, China; Peking-Tsinghua Center for Life Sciences, Beijing, China; Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.
  • 6 State Key Laboratory of Membrane Biology and Beijing Key Laboratory of Cardio-metabolic Molecular Medicine, Peking University, Beijing, China.
  • 7 Department of Dermatology, Peking University Third Hospital, Beijing, China.
  • 8 Center for the Study of Itch and Sensory Disorders, Washington University School of Medicine, St. Louis, USA; Department of Dermatology(,) Washington University School of Medicine, St. Louis, USA.
  • 9 Department of Dermatology, Peking University First Hospital, Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, National Clinical Research Center for Skin and Immune Disease, Beijing, China; Peking-Tsinghua Center for Life Sciences, Beijing, China; Current Address: Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China. Electronic address: yyang@pumcderm.cams.cn.
  • 10 Center for the Study of Itch and Sensory Disorders, Washington University School of Medicine, St. Louis, USA; Department of Anesthesiology, Washington University School of Medicine, St. Louis, USA; Department of Psychiatry, Washington University School of Medicine, St. Louis, USA; Department of Developmental Biology, Washington University School of Medicine, St. Louis, USA. Electronic address: chenz@morpheus.wustl.edu.
PMID: 32004565 DOI: 10.1016/j.jid.2020.01.012
Abstract

Animal studies have suggested that transient receptor potential ion channels and G-protein coupled receptors 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, whereas their inhibition attenuated scratching and inflammatory responses in mouse atopic Dermatitis Models. 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 atopic dermatitis.

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