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. 2025 Dec;182(23):5814-5825.
doi: 10.1111/bph.70153. Epub 2025 Aug 6.

TRPA1 ion channel activation context-dependently regulates gene expression in normal and psoriatic human skin

Ágnes Kemény  1   2 , Szabina Horváth  3 , Júlia Szebényi  3 , Péter Oláh  3   4 , Viktória Németh  3 , Péter Urbán  5 , József Kun  1   5   6 , Attila Gyenesei  5 , Areej Jaber  1   3 , Erika Pintér  1 , Rolland Gyulai  3   7
Affiliations

TRPA1 ion channel activation context-dependently regulates gene expression in normal and psoriatic human skin

Ágnes Kemény et al. Br J Pharmacol. 2025 Dec.

Abstract

Background and purpose: Psoriasis is a chronic, relapsing, immune-mediated inflammatory skin disease. The transient receptor potential ankyrin 1 (TRPA1) ion channel plays a protective role in the formation of psoriasiform skin reactions. Here, we investigated the pharmacological activation and blockade of TRPA1 in human skin (patho)physiology.

Experimental approach: Six-millimetre full-thickness biopsies were obtained from psoriatic lesional and non-lesional skin of four patients with psoriasis, and from normal skin of four healthy volunteers. Each biopsy was quartered: One segment was untreated, and the other three were cultured with vehicle (DMSO), TRPA1 agonist mustard oil (MO), or TRPA1 antagonist (HC030031), respectively. Global gene expression was measured by RNA sequencing, followed by differential expression and functional enrichment analyses, to identify TRPA1-modulated genes.

Key results: Pre-evaluation of data with ordination assessment showed clear cluster formation according to treatments and condition of the skin. In healthy skin, TRPA1 activation down-regulated genes associated with interferon signalling, antimicrobial responses, and inflammation/oxidative stress. In lesional psoriatic skin, the genes of interleukin-4 (IL-4), IL-10 and IL-13 cytokine signalling-related proteins, circadian gene expression, and senescence-associated secretory phenotype (SASP) genes were down-regulated by MO treatment. Antagonist treatment did not cause significant gene expression changes, supporting the previous finding that basal TRPA1 activity is low in the skin. DMSO treatment in all three conditions increased expression of several inflammatory genes, which was normalised during data analysis.

Conclusion and implications: Exploration of the interactions between TRPA1 and identified signalling pathways may open new opportunities to target psoriasis, alleviate disease symptoms and optimise therapies.

Keywords: RNA sequencing; human skin tissue culture; psoriasis; transient receptor potential ankyrin 1.

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References

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