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


OBJECTIVE
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.
Department of Dermatology, Chiba Aoba Municipal Hospital, 1273-2 Aoba-cho, Chuo-ku, Chiba 260-0852, Japan. chw92121@syd.odn.ne.jp
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Endo
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Momota
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Oikawa
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Shinkai
D002460:Cell Line; D006801:Humans; D007124:Immunoenzyme Techniques; D015603:Keratinocytes / Q000378:metabolism; D025542:Neurofibromin 1 / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000378:metabolism*; D011565:Psoriasis / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D012867:Skin / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D000071676:Zinc Finger Protein GLI1
C400551:GLI1 protein, human; D025542:Neurofibromin 1; D012333:RNA, Messenger; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1