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 adaptive inflammatory cellular immune responses is considered to be the main trigg...

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Main Authors: Kristina Leuner, Margarethe Kraus, Ute Woelfle, Heike Beschmann, Christian Harteneck, Wolf-Henning Boehncke, Christoph M Schempp, Walter E Müller
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2011-02-01
Series:PLoS ONE
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21364982/?tool=EBI
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spelling doaj-4bc0101458954322b97b6b1c5ddeb2e12021-03-04T02:04:19ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-02-0162e1471610.1371/journal.pone.0014716Reduced TRPC channel expression in psoriatic keratinocytes is associated with impaired differentiation and enhanced proliferation.Kristina LeunerMargarethe KrausUte WoelfleHeike BeschmannChristian HarteneckWolf-Henning BoehnckeChristoph M SchemppWalter E MüllerPsoriasis 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 Ca(2+). In normal epidermis, a Ca(2+) 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 [Ca(2+)](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 Ca(2+) influx in psoriatic keratinocytes in response to high extracellular Ca(2+) levels, associated with a downregulation of all TRPC channels investigated, including TRPC6 channels. As TRPC6 channel activation can partially overcome this Ca(2+) entry defect, specific TRPC channel activators may be potential new drug candidates for the topical treatment of psoriasis.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21364982/?tool=EBI
collection DOAJ
language English
format Article
sources DOAJ
author Kristina Leuner
Margarethe Kraus
Ute Woelfle
Heike Beschmann
Christian Harteneck
Wolf-Henning Boehncke
Christoph M Schempp
Walter E Müller
spellingShingle Kristina Leuner
Margarethe Kraus
Ute Woelfle
Heike Beschmann
Christian Harteneck
Wolf-Henning Boehncke
Christoph M Schempp
Walter E Müller
Reduced TRPC channel expression in psoriatic keratinocytes is associated with impaired differentiation and enhanced proliferation.
PLoS ONE
author_facet Kristina Leuner
Margarethe Kraus
Ute Woelfle
Heike Beschmann
Christian Harteneck
Wolf-Henning Boehncke
Christoph M Schempp
Walter E Müller
author_sort Kristina Leuner
title Reduced TRPC channel expression in psoriatic keratinocytes is associated with impaired differentiation and enhanced proliferation.
title_short Reduced TRPC channel expression in psoriatic keratinocytes is associated with impaired differentiation and enhanced proliferation.
title_full Reduced TRPC channel expression in psoriatic keratinocytes is associated with impaired differentiation and enhanced proliferation.
title_fullStr Reduced TRPC channel expression in psoriatic keratinocytes is associated with impaired differentiation and enhanced proliferation.
title_full_unstemmed Reduced TRPC channel expression in psoriatic keratinocytes is associated with impaired differentiation and enhanced proliferation.
title_sort reduced trpc channel expression in psoriatic keratinocytes is associated with impaired differentiation and enhanced proliferation.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2011-02-01
description 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 Ca(2+). In normal epidermis, a Ca(2+) 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 [Ca(2+)](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 Ca(2+) influx in psoriatic keratinocytes in response to high extracellular Ca(2+) levels, associated with a downregulation of all TRPC channels investigated, including TRPC6 channels. As TRPC6 channel activation can partially overcome this Ca(2+) entry defect, specific TRPC channel activators may be potential new drug candidates for the topical treatment of psoriasis.
url https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21364982/?tool=EBI
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