ArticleThe Journal of investigative dermatology2011
Inhibition of transcription factor specificity protein 1 alters the gene expression profile of keratinocytes leading to upregulation of kallikrein-related peptidases and thymic stromal lymphopoietin.
Article in The Journal of investigative dermatology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 26 citations in OpenAlex.
- Herpes simplex virus and kallikrein-related peptidases - a functional connection in Alzheimer's disease.Alzheimer's research & therapy · 2026Article
- Ovol1/2 loss-induced epidermal defects elicit skin immune activation and alter global metabolism.EMBO reports · 2023Article
- Regulation of Tissue Factor by CD44 Supports Coagulant Activity in Breast Tumor Cells.Cancers · 2022Article
- The Keratinocyte as a Crucial Cell in the Predisposition, Onset, Progression, Therapy and Study of the Atopic Dermatitis.International journal of molecular sciences · 2021Review
- Transcriptional Suppression of miR-7 by MTA2 Induces Sp1-Mediated KLK10 Expression and Metastasis of Cervical Cancer.Molecular therapy. Nucleic acids · 2020Article
- Role of bulge epidermal stem cells and TSLP signaling in psoriasis.EMBO molecular medicine · 2019Article
- Loss of kallikrein-related peptidase 7 exacerbates amyloid pathology in Alzheimer's disease model mice.EMBO molecular medicine · 2018Article
- Zinc in Keratinocytes and Langerhans Cells: Relevance to the Epidermal Homeostasis.Journal of immunology research · 2018Review
- Discovery of Novel Human Gene Regulatory Modules from Gene Co-expression and Promoter Motif Analysis.Scientific reports · 2017Article
- The regulatory mechanisms of NG2/CSPG4 expression.Cellular & molecular biology letters · 2017Review
- Unleashing the therapeutic potential of human kallikrein-related serine proteases.Nature reviews. Drug discovery · 2015Review
- Functions of thymic stromal lymphopoietin in immunity and disease.Immunologic research · 2012Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Transcription factor specificity protein 1 (Sp1) is involved in diverse cellular functions. We recently found that Sp1 was significantly decreased in skin biopsy samples obtained from patients with atopic dermatitis (AD) and had an even greater reduction in AD patients with a history of eczema herpeticum. In the current study, we sought to better understand the role of Sp1 in skin biological processes by using a small-interfering RNA (siRNA) technique to knock down Sp1 gene expression in normal human keratinocytes (NHKs) and investigated the genome-wide gene expression profiling of Sp1-silenced NHKs. The gene arrays revealed that 53 genes had greater than 3-fold changes in the expression in Sp1-silenced NHKs as compared with scrambled siRNA-silenced cells. Strikingly, six kallikrein (KLK)-related peptidase genes, namely KLK5, KLK6, KLK7, KLK8, KLK10, and KLK12, were upregulated in NHKs following Sp1 silencing. Functionally, protease activity was significantly enhanced in Sp1-silenced keratinocytes as compared with scrambled siRNA-silenced keratinocytes. Moreover, thymic stromal lymphopoietin (TSLP), an epithelial-derived T(H)2-promoting cytokine, was induced in Sp1-silenced keratinocytes because of elevated KLK activity. These results indicate that Sp1 expression deficiency leads to abnormally increased KLK protease activity in keratinocytes and may contribute to T(H)2 immune responses in the skin by inducing TSLP.
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