Regulatory role for Krüppel-like zinc-finger protein Gli-similar 1 (Glis1) in PMA-treated and psoriatic epidermis.
In this study, we analyze the expression and potential function of the Krüppel-like zinc-finger protein Gli-similar protein 1 (Glis1) in normal and inflammatory skin and in the differentiation of epidermal keratinocytes. Glis1 mRNA is not expressed in normal human epidermis, but is significantly induced in psoriatic epidermis and in mouse skin upon treatment with the tumor promoter phorbol-12-myristate-13-acetate (PMA). The expression of Glis1 is restricted to the suprabasal layers. These observations suggest that Glis1 expression is associated with hyperplastic, inflammatory epidermis. Consistent with these findings, Glis1 mRNA is not expressed in undifferentiated or differentiated normal human epidermal keratinocytes (NHEK) in culture, but is dramatically induced after the addition of PMA or interferon gamma. A similar induction of Glis1 mRNA by PMA treatment was observed in the immortalized epidermal keratinocyte cell line NHEK-HPV, whereas PMA did not induce Glis1 in HaCaT cells or in several squamous cell carcinoma cell lines. To obtain insight into its function, Glis1 and a C-terminal deletion mutant Glis1DeltaC were expressed in NHEK-HPV cells and changes in epidermal differentiation and gene expression examined. Microarray analysis revealed that Glis1DeltaC promoted PMA-induced epidermal differentiation, as indicated by increased expression of many differentiation-specific genes. This, in association with its induction in psoriasis, suggests that transcriptional factor Glis1 is involved in the regulation of aberrant differentiation observed in psoriatic epidermis.
Nakanishi
Gen
G
Cell Biology Section, Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA.
Kim
Yong-Sik
YS
Nakajima
Takeshi
T
Jetten
Anton M
AM
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002467:Cell Nucleus / Q000737:chemistry; D002478:Cells, Cultured; D003593:Cytoplasm / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism* / Q000473:pathology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009154:Mutation; D011565:Psoriasis / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D017384:Sequence Deletion; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000494:pharmacology; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; C508055:GLIS1 protein, human; D012333:RNA, Messenger; D014157:Transcription Factors; C016658:phorbolol myristate acetate; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate