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Lymphocyte Isolation from Human Skin for Phenotypic Analysis and Ex Vivo Cell Culture
Published on: April 8, 2016
Genomic-scale analysis of psoriatic skin reveals differentially expressed insulin-like growth factor-binding
M Hochberg1, S Zeligson, N Amariglio
1Department of Dermatology, Hadassah Hebrew University Medical School, IL-91010 Jerusalem, Israel. malka@hadassah.org.il
Background:
Phototherapy is an effective therapy for psoriasis. The molecular mechanisms underlying its efficacy are not yet understood.
Objectives:
To compare the expression profiles of psoriatic epidermis in patients before and after undergoing phototherapy with the purpose of expounding the molecular mechanisms underlying the efficacy of this therapeutic modality.
Methods:
Patients with psoriasis were investigated before and after full courses of phototherapy: three patients completed 3 weeks of heliotherapy at the Dead Sea; three patients received narrowband ultraviolet B (NB-UVB) for a total of 20-27 treatments. Epidermal samples were analysed using oligonucleotide microarrays. Our microarray results led us to explore further and to quantify a specific gene, insulin-like growth factor-binding protein-7 (IGFBP7), using real-time quantitative reverse transcriptase-polymerase chain reaction assays and immunohistochemical protein expression.
Results:
We identified 315 genes modulated by phototherapy: the expressions of 248 genes (142 up; 106 down) were changed by Dead Sea treatment, 116 (71 up; 45 down) by NB-UVB and 49 (37 up; 12 down) were modulated regardless of treatment. The differentially changed genes include S100 calcium-binding proteins, dendritic cell markers, tumour necrosis factor-alpha target genes, matrix metalloproteinases and NFkappaB target genes. We also found that IGFBP7 mRNA and protein were significantly underexpressed in psoriatic compared with normal epidermis, and that phototherapy significantly increased their expression.
Conclusions:
IGFBP7 is underexpressed in psoriatic epidermis but is inducible by UVB.
Insights
Phototherapy effectively treats psoriasis by altering gene expression. This study found insulin-like growth factor-binding protein-7 (IGFBP7) is underexpressed in psoriasis but increases with UVB treatment.
Area of Science:
- Dermatology and Molecular Biology
- Photomedicine
Background:
- Phototherapy is a recognized treatment for psoriasis.
- The precise molecular mechanisms driving phototherapy's effectiveness remain unclear.
Purpose of the Study:
- To investigate molecular changes in psoriatic epidermis post-phototherapy.
- To elucidate the mechanisms behind phototherapy's efficacy in psoriasis treatment.
Main Methods:
- Oligonucleotide microarrays were used to analyze epidermal gene expression profiles before and after phototherapy (Dead Sea heliotherapy and narrowband ultraviolet B).
- Insulin-like growth factor-binding protein-7 (IGFBP7) expression was further quantified using real-time PCR and immunohistochemistry.
Main Results:
- Phototherapy modulated 315 genes, with distinct changes observed for Dead Sea treatment and narrowband UVB.
- Key modulated genes included S100 calcium-binding proteins, dendritic cell markers, and TNF-alpha target genes.
- Insulin-like growth factor-binding protein-7 (IGFBP7) mRNA and protein were significantly upregulated by phototherapy, despite being underexpressed in psoriatic skin.
Conclusions:
- Insulin-like growth factor-binding protein-7 (IGFBP7) is downregulated in psoriatic epidermis.
- UVB phototherapy can induce the expression of IGFBP7 in psoriatic skin, suggesting a role in treatment efficacy.