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Original Article

Korean Journal of Physiology and Pharmacology 2019; 23(2): 151-159

Published online March 1, 2019 https://doi.org/10.4196/kjpp.2019.23.2.151

Copyright © The Korean Journal of Physiology & Pharmacology.

Prediction of itching diagnostic marker through RNA sequencing of contact hypersensitivity and skin scratching stimulation mice models

Young-Won Kim1, Tong Zhou2, Eun-A Ko2, Seongtae Kim1, Donghee Lee1, Yelim Seo1, Nahee Kwon3, Taeyeon Choi3, Heejung Lim3, Sungvin Cho3, Gwanhui Bae3, Yuseong Hwang3, Dojin Kim3, Hyewon Park3, Minjae Lee3, Eunkyung Jang3, Jeongyoon Choi1, Hyemi Bae1, Inja Lim1, Hyoweon Bang1,*, and Jae-Hong Ko1,*

1Department of Physiology, Chung-Ang University College of Medicine, Seoul 06974, Korea, 2Department of Physiology and Cell Biology, University of Nevada, Reno School of Medicine, Reno, NV 89557, USA, 3Department of Medicine, Chung-Ang University College of Medicine, Seoul 06974, Korea

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Pruritus (itching) is classically defined as an unpleasant cutaneous sensation that leads to scratching behavior. Although the scientific criteria of classification for pruritic diseases are not clear, it can be divided as acute or chronic by duration of symptoms. In this study, we investigated whether skin injury caused by chemical (contact hypersensitivity, CHS) or physical (skin-scratching stimulation, SSS) stimuli causes initial pruritus and analyzed gene expression profiles systemically to determine how changes in skin gene expression in the affected area are related to itching. In both CHS and SSS, we ranked the Gene Ontology Biological Process terms that are generally associated with changes. The factors associated with upregulation were keratinization, inflammatory response and neutrophil chemotaxis. The Kyoto Encyclopedia of Genes and Genomes pathway shows the difference of immune system, cell growth and death, signaling molecules and interactions, and signal transduction pathways. Il1a , Il1b and Il22 were upregulated in the CHS, and Tnf , Tnfrsf1b, Il1b, Il1r1 and Il6 were upregulated in the SSS. Trpc1 channel genes were observed in representative itching-related candidate genes. By comparing and analyzing RNA-sequencing data obtained from the skin tissue of each animal model in these characteristic stages, it is possible to find useful diagnostic markers for the treatment of itching, to diagnose itching causes and to apply customized treatment.

Keywords: Cytokines, Pruritus, RNA sequence analysis, Transient receptor potential channels, Wound healing