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

Köhler , Ralf
Society for Investigative Dermatology
Participation type: 
Other authors: 
Yolanda Gilaberte, Javier Lozano-Gerona, Aida Oliván-Viguera, Pablo Delgado-Wicke, Vikrant Singh, Brandon M. Brown, Elena Tapia-Casellas, Esther Pueyo, Marta Sofía Valero, Ángel-Luis Garcia-Otín, Pilar Giraldo, Edgar Abarca-Lachen, Joaquín C. Surra, Jesús Osada, Kirk L. Hamilton, Siba P. Raychaudhuri, Miguel Marigil, Ángeles Juarranz, Heike Wulff, Hiroto Miura
Chicago IL
KCa3.1-overexpression in skin causes pruritic eczema and epidermal hyperplasia J. Lozano-Gerona, A. Olivan-Viguera, P. Delgado-Wicke, V. Singh, B. Brown, E. Tapia-Casellas, E. Pueyo, M.S. Valero, and others Journal of Investigative Dermatology, Vol. 139, Issue 5, S51 Published in issue: May 2019

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. In-vivo treatment with the KCa3.1-selective blocker, Senicapoc, significantly suppressed spongiosis, hyperplasia, and induction of IL-β1 (-88%), IL-23 (-77%), and IL-6 (-90%). In conclusion, KCa3.1-induction over basal levels in keratinocytes resulted in expression of several pro-proliferative and pro-inflammatory cytokines, spongiosis, hyperplasia, and hyperkeratosis, itch, and morbidity. This skin condition is similar to eczematous and psoriasiform dermatitis and identifies KCa3.1 as a key player in epidermal homeostasis and spongiosis. Clinically safe KCa3.1-blockers may be of therapeutic utility to treat spongiosis and itchy eczematous dermatitis.