Unknown

Dataset Information

0

Conditional KCa3.1-transgene induction in murine skin produces pruritic eczematous dermatitis with severe epidermal hyperplasia and hyperkeratosis.


ABSTRACT: Ion channels have recently attracted attention as potential mediators of 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. Doxycycline-treated mice harboring the KCa3.1+-transgene under the control of the reverse tetracycline-sensitive transactivator (rtTA) showed 800-fold channel overexpression above basal levels in the skin and solid KCa3.1-currents in keratinocytes. This overexpression resulted in epidermal spongiosis, progressive epidermal hyperplasia and hyperkeratosis, itch and ulcers. The condition was accompanied by production of the pro-proliferative and pro-inflammatory cytokines, IL-?1 (60-fold), IL-6 (33-fold), and TNF? (26-fold) in the skin. Treatment of mice with the KCa3.1-selective blocker, Senicapoc, significantly suppressed spongiosis and hyperplasia, as well as induction of IL-?1 (-88%) and IL-6 (-90%). In conclusion, KCa3.1-induction in the epidermis caused expression of pro-proliferative cytokines leading to spongiosis, hyperplasia and hyperkeratosis. This skin condition resembles pathological features of eczematous dermatitis and identifies KCa3.1 as a regulator of epidermal homeostasis and spongiosis, and as a potential therapeutic target.

SUBMITTER: Lozano-Gerona J 

PROVIDER: S-EPMC7062274 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

altmetric image

Publications


Ion channels have recently attracted attention as potential mediators of 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. Doxycycline-treated mice harboring the KCa3.1+-transgene under the control of the reverse tetracycline-sensitive transactivator (rtTA) showed 800-fold channel overexpression above basal levels in the skin and solid KCa3.1-currents in keratinoc  ...[more]

Similar Datasets

| S-EPMC8124688 | biostudies-literature
| S-EPMC7549904 | biostudies-literature
| S-EPMC515354 | biostudies-literature
| S-EPMC4887165 | biostudies-literature
| S-EPMC7239756 | biostudies-literature
| S-EPMC4007207 | biostudies-literature
2021-12-01 | GSE159704 | GEO
| S-EPMC55386 | biostudies-literature
| S-EPMC6212948 | biostudies-literature
| S-EPMC4074411 | biostudies-literature