TY  - JOUR
A1  - Leuner, Kristina
A1  - Kraus, Margarethe
A1  - Wölfle, Ute
A1  - Beschmann, Heike A.
A1  - Harteneck, Christian
A1  - Boehncke, Wolf-Henning
A1  - Schempp, Christoph Mathis
A1  - Müller, Walter E.
T1  - Reduced TRPC channel expression in psoriatic keratinocytes is associated with impaired differentiation and enhanced proliferation
T2  - PLoS One
N2  - Psoriasis is a characteristic inflammatory and scaly skin condition with typical histopathological features including increased proliferation and hampered differentiation of keratinocytes. The activation of innate and adaptive inflammatory cellular immune responses is considered to be the main trigger factor of the epidermal changes in psoriatic skin. However, the molecular players that are involved in enhanced proliferation and impaired differentiation of psoriatic keratinocytes are only partly understood. One important factor that regulates differentiation on the cellular level is Ca2+. In normal epidermis, a Ca2+ gradient exists that is disturbed in psoriatic plaques, favoring impaired keratinocyte proliferation. Several TRPC channels such as TRPC1, TRPC4, or TRPC6 are key proteins in the regulation of high [Ca2+]ex induced differentiation. Here, we investigated if TRPC channel function is impaired in psoriasis using calcium imaging, RT-PCR, western blot analysis and immunohistochemical staining of skin biopsies. We demonstrated substantial defects in Ca2+ influx in psoriatic keratinocytes in response to high extracellular Ca2+ levels, associated with a downregulation of all TRPC channels investigated, including TRPC6 channels. As TRPC6 channel activation can partially overcome this Ca2+ entry defect, specific TRPC channel activators may be potential new drug candidates for the topical treatment of psoriasis.
Y1  - 2011
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/22583
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30-114344
SN  - 1932-6203
N1  - Copyright: © 2011 Leuner et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
VL  - 6
IS  - (2): e14716
ER  -