297 KCa3.1-overexpression in skin causes pruritic eczema and epidermal hyperplasia

Ion channels have emerged as potential mediators of chronic skin disease. Here, we explored the consequences of genetically encoded induction of the cell volume-regulating Ca2+-activated KCa3.1 channel (Kcnn4) for murine epidermal homeostasis. 800-fold channel overexpression in keratinocytes of doxycycline-treated KCa3.1+ mice produced strong KCa3.1-functions, epidermal spongiosis, progressive epidermal hyperplasia, hyperkeratosis, itch and ulcers, and high morbidity within two weeks. We found significant induction of pro-proliferative and pro-inflammatory cytokines, IL- β1 (60-fold over basal levels), IL-23 (34-fold), IL-6 (33-fold), and TNFα (26-fold) in the skin.

Source: Journal of Investigative Dermatology - April 19, 2019 Category: Dermatology Authors: J. Lozano-Gerona, A. Olivan-Viguera, P. Delgado-Wicke, V. Singh, B. Brown, E. Tapia-Casellas, E. Pueyo, M.S. Valero, A.L. Garc ía-Otin, P. Giraldo, E. Abarca-Lachen, J. Surra, J. Osada, K. Hamilton, M. Marigil, A. Juarranz, H. Wulff, H. Miura, Y. Gilaber Tags: Epidermal Structure and Barrier Function Source Type: research