Reduced TRPC channel expression in psoriatic keratinocytes is associated with impaired differentiation and enhanced proliferation

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 ad
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.
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Metadaten
Author:Kristina Leuner, Margarethe Kraus, Ute Woelfle, Heike A. Beschmann, Christian Harteneck, Wolf-Henning Boehncke, Christoph Mathis Schempp, Walter E. Müller
URN:urn:nbn:de:hebis:30-114344
DOI:http://dx.doi.org/10.1371/journal.pone.0014716
ISSN:1932-6203
Parent Title (English):PLoS one
Document Type:Article
Language:English
Date of Publication (online):2011/09/02
Year of first Publication:2011
Publishing Institution:Univ.-Bibliothek Frankfurt am Main
Release Date:2011/09/02
Note:
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.
Source:PLoS ONE 6(2): e14716. doi: 10.1371/journal.pone.0014716
HeBIS PPN:276019474
Institutes:Pharmazie
Medizin
Dewey Decimal Classification:610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 3.0

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