Growing evidence indicates that transient receptor potential (TRP) channels contribute to different forms of pruritus. However, the endogenous mediators that cause itch via TRP channels signaling are poorly understood. Herein, we show that genetic deletion or pharmacological antagonism of TRP vanilloid 4 (TRPV4) attenuated itch in a mouse model of psoriasis induced by topical application of imiquimod. Human psoriatic lesions showed increased expression of several miRNAs, including the miR-203b-3p, which induced a Ca2+ response in rodent dorsal root ganglion neurons and scratching behavior in mice via serotonin receptor 2B (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 miRNA that can behave as an itch promoter via 5-HTR2B and TRPV4.

miRNA-203b-3p induces acute and chronic pruritus via 5-HTR2B and TRPV4 / De Logu, Francesco; Maglie, Roberto; Titiz, Mustafa; Poli, Giulio; Landini, Lorenzo; Marini, Matilde; Monteiro de Araujo, Daniel Souza; De Siena, Gaetano; Montini, Marco; Cabrini, Daniela Almeida; Otuki, Michel Fleith; Pawloski, Priscila Lúcia; Antiga, Emiliano; Tuccinardi, Tiziano; Calixto, João Batista; Geppetti, Pierangelo; Nassini, Romina; André, Eunice. - In: JOURNAL OF INVESTIGATIVE DERMATOLOGY. - ISSN 0022-202X. - ELETTRONICO. - (2022), pp. 0-0. [10.1016/j.jid.2022.08.034]

miRNA-203b-3p induces acute and chronic pruritus via 5-HTR2B and TRPV4

De Logu, Francesco;Maglie, Roberto;Titiz, Mustafa;Marini, Matilde;Monteiro de Araujo, Daniel Souza;De Siena, Gaetano;Montini, Marco;Antiga, Emiliano;Geppetti, Pierangelo;Nassini, Romina
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2022

Abstract

Growing evidence indicates that transient receptor potential (TRP) channels contribute to different forms of pruritus. However, the endogenous mediators that cause itch via TRP channels signaling are poorly understood. Herein, we show that genetic deletion or pharmacological antagonism of TRP vanilloid 4 (TRPV4) attenuated itch in a mouse model of psoriasis induced by topical application of imiquimod. Human psoriatic lesions showed increased expression of several miRNAs, including the miR-203b-3p, which induced a Ca2+ response in rodent dorsal root ganglion neurons and scratching behavior in mice via serotonin receptor 2B (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 miRNA that can behave as an itch promoter via 5-HTR2B and TRPV4.
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De Logu, Francesco; Maglie, Roberto; Titiz, Mustafa; Poli, Giulio; Landini, Lorenzo; Marini, Matilde; Monteiro de Araujo, Daniel Souza; De Siena, Gaetano; Montini, Marco; Cabrini, Daniela Almeida; Otuki, Michel Fleith; Pawloski, Priscila Lúcia; Antiga, Emiliano; Tuccinardi, Tiziano; Calixto, João Batista; Geppetti, Pierangelo; Nassini, Romina; André, Eunice
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2158/1282279
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