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Psoriatic skin expresses the transcription factor Gli1: possible contribution of decreased neurofibromin expression

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Summary Background 

Psoriasis is a chronic inflammatory disorder of skin characterized by hyperproliferation of keratinocytes. Intracellular signalling pathways inducing the hyperproliferation of keratinocytes remain to be elucidated. An inhibitor of Hedgehog (Hh) signalling, cyclopamine, was recently reported to clear psoriatic skin lesions, suggesting involvement of the Hh signalling pathway in the hyperproliferation of lesional keratinocytes. We have previously observed activation of the Hh signalling pathway in Schwann cells of plexiform neurofibroma in neurofibromatosis type 1 (NF1), which results from functional loss of the NF1 encoding protein, neurofibromin. In psoriasis, deficiency of neurofibromin expression has been observed in lesional keratinocytes. Objectives 

To investigate whether the Hh signalling pathway would be activated in psoriasis and whether inhibition of neurofibromin expression would enhance the activation of the Hh signalling pathway. Methods 

Activation of the Hh signalling pathway was examined by protein expression of one of the target genes, GLI1, coding for the transcription factor Gli1. Immunohistochemical studies were performed on seven psoriatic skin samples and seven control normal skin samples with a standard immunoperoxidase technique. mRNA expression of GLI1 was analysed by reverse transcriptase–polymerase chain reaction in HaCaT cells transfected with double-strand small interfering RNA for NF1. Results 

Our results showed Gli1 expression in psoriatic skin but not in control normal skin. Inhibition of neurofibromin expression in HaCaT cells upregulated mRNA expression of GLI1. Conclusions 

Our findings indicate that the Hh signalling pathway is activated in psoriasis and that neurofibromin deficiency may upregulate the pathway.
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Keywords: Gli1; Hedgehog; keratinocytes; neurofibromin; psoriasis

Document Type: Research Article

Affiliations: Department of Clinical Biology of Extracellular Matrix, Graduate School of Medicine, Chiba University, Chiba, Japan

Publication date: 2006-04-01

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