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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Autores principales:	Kristina Leuner, Margarethe Kraus, Ute Woelfle, Heike Beschmann, Christian Harteneck, Wolf-Henning Boehncke, Christoph M Schempp, Walter E Müller
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4bc0101458954322b97b6b1c5ddeb2e1
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spelling	oai:doaj.org-article:4bc0101458954322b97b6b1c5ddeb2e12021-11-18T06:58:27ZReduced TRPC channel expression in psoriatic keratinocytes is associated with impaired differentiation and enhanced proliferation.1932-620310.1371/journal.pone.0014716https://doaj.org/article/4bc0101458954322b97b6b1c5ddeb2e12011-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21364982/?tool=EBIhttps://doaj.org/toc/1932-6203Psoriasis 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.Kristina LeunerMargarethe KrausUte WoelfleHeike BeschmannChristian HarteneckWolf-Henning BoehnckeChristoph M SchemppWalter E MüllerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 2, p e14716 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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.
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.
format	article
author	Kristina Leuner Margarethe Kraus Ute Woelfle Heike Beschmann Christian Harteneck Wolf-Henning Boehncke Christoph M Schempp Walter E Müller
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)
publishDate	2011
url	https://doaj.org/article/4bc0101458954322b97b6b1c5ddeb2e1
work_keys_str_mv	AT kristinaleuner reducedtrpcchannelexpressioninpsoriatickeratinocytesisassociatedwithimpaireddifferentiationandenhancedproliferation AT margarethekraus reducedtrpcchannelexpressioninpsoriatickeratinocytesisassociatedwithimpaireddifferentiationandenhancedproliferation AT utewoelfle reducedtrpcchannelexpressioninpsoriatickeratinocytesisassociatedwithimpaireddifferentiationandenhancedproliferation AT heikebeschmann reducedtrpcchannelexpressioninpsoriatickeratinocytesisassociatedwithimpaireddifferentiationandenhancedproliferation AT christianharteneck reducedtrpcchannelexpressioninpsoriatickeratinocytesisassociatedwithimpaireddifferentiationandenhancedproliferation AT wolfhenningboehncke reducedtrpcchannelexpressioninpsoriatickeratinocytesisassociatedwithimpaireddifferentiationandenhancedproliferation AT christophmschempp reducedtrpcchannelexpressioninpsoriatickeratinocytesisassociatedwithimpaireddifferentiationandenhancedproliferation AT walteremuller reducedtrpcchannelexpressioninpsoriatickeratinocytesisassociatedwithimpaireddifferentiationandenhancedproliferation
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Reduced TRPC channel expression in psoriatic keratinocytes is associated with impaired differentiation and enhanced proliferation.

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