miRNA-203b-3p Induces Acute and Chronic Pruritus through 5-HTR2B and TRPV4.

The Journal of investigative dermatology 2023 Jan

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Growing evidence indicates that transient receptor potential (TRP) channels contribute to different forms of pruritus. However, the endogenous mediators that cause itch through transient receptor potential channels signaling are poorly understood. In this study, we show that genetic deletion or pharmacological antagonism of TRPV4 attenuated itch in a mouse model of psoriasis induced by topical application of imiquimod. Human psoriatic lesions showed increased expression of several microRNAs, including the miR-203b-3p, which induced a calcium ion response in rodent dorsal root ganglion neurons and scratching behavior in mice through 5-HTR2B activation and the protein kinase C‒dependent phosphorylation of TRPV4. Computer simulation revealed that the miR-203b-3p core sequence (GUUAAGAA) that causes 5-HTR2B/TRPV4-dependent itch targets the extracellular side of 5-HTR2B by interacting with a portion of the receptor pocket consistent with its activation. Overall, we reveal the unconventional pathophysiological role of an extracellular microRNA that can behave as an itch promoter through 5-HTR2B and TRPV4. Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Francesco De Logu, Roberto Maglie, Mustafa Titiz, Giulio Poli, Lorenzo Landini, Matilde Marini, Daniel Souza Monteiro de Araujo, Gaetano De Siena, Marco Montini, Daniela Almeida Cabrini, Michel Fleith Otuki, Priscila Lúcia Pawloski, Emiliano Antiga, Tiziano Tuccinardi, João Batista Calixto, Pierangelo Geppetti, Romina Nassini, Eunice André. miRNA-203b-3p Induces Acute and Chronic Pruritus through 5-HTR2B and TRPV4. The Journal of investigative dermatology. 2023 Jan;143(1):142-153.e10