Project description:We studied the transcriptomic profile of actinic keratosis (AK) skin compared to matched samples from uninvolved skin (US) before and after treatment with ingenol mebutate gel. We found that AK has a distinct mRNA profile that separates it from uninvolved skin. In particular, numerous genes associated with epidermal development and keratinocyte differentiation, such as LCE3D, SPRR1A, PI3 and several genes in the keratin family were highly expressed in AK0 skin, but not in US0, in line with the hyperkeratosis characteristic for AK. Topical application of ingenol mebutate had a profound effect on the gene expression profile, and interestingly, many more genes were affected in US than in AK. Enrichment analysis revealed that the main responses to ingenol mebutate treatment of both US and AK were inflammatory response, response to wounding, and wound healing. 30 skin biopsies were analysed; 5 from each of 6 AK patients. Before initiation of treatment, baseline biopsies were taken from one AK lesion (AK0) and from uninvolved skin (US0). A third biopsy was taken after day 1 application of ingenol mebutate from one AK lesion (AK1). The fourth and fifth biopsies were obtained one day after the second topical application with ingenol mebutate from an AK lesion (AK2) and from uninvolved skin (US2), respectively.
Project description:Actinic keratosis is a common skin disease that may progress to invasive squamous cell carcinoma. Ingenol mebutate has demonstrated efficacy in field treatment of actinic keratosis. However, molecular mechanisms on ingenol mebutate response are not yet fully understood.
Project description:We studied the transcriptomic profile of actinic keratosis (AK) skin compared to matched samples from uninvolved skin (US) before and after treatment with ingenol mebutate gel. We found that AK has a distinct mRNA profile that separates it from uninvolved skin. In particular, numerous genes associated with epidermal development and keratinocyte differentiation, such as LCE3D, SPRR1A, PI3 and several genes in the keratin family were highly expressed in AK0 skin, but not in US0, in line with the hyperkeratosis characteristic for AK. Topical application of ingenol mebutate had a profound effect on the gene expression profile, and interestingly, many more genes were affected in US than in AK. Enrichment analysis revealed that the main responses to ingenol mebutate treatment of both US and AK were inflammatory response, response to wounding, and wound healing.
Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs.
Project description:Transcriptional profiling of Homo sapiens inflammatory skin diseases (whole skin biospies): Psoriasis (Pso), vs Atopic Dermatitis (AD) vs Lichen planus (Li), vs Contact Eczema (KE), vs Healthy control (KO) In recent years, different genes and proteins have been highlighted as potential biomarkers for psoriasis, one of the most common inflammatory skin diseases worldwide. However, most of these markers are not psoriasis-specific but also found in other inflammatory disorders. We performed an unsupervised cluster analysis of gene expression profiles in 150 psoriasis patients and other inflammatory skin diseases (atopic dermatitis, lichen planus, contact eczema, and healthy controls). We identified a cluster of IL-17/TNFα-associated genes specifically expressed in psoriasis, among which IL-36γ was the most outstanding marker. In subsequent immunohistological analyses IL-36γ was confirmed to be expressed in psoriasis lesions only. IL-36γ peripheral blood serum levels were found to be closely associated with disease activity, and they decreased after anti-TNFα-treatment. Furthermore, IL-36γ immunohistochemistry was found to be a helpful marker in the histological differential diagnosis between psoriasis and eczema in diagnostically challenging cases. These features highlight IL-36γ as a valuable biomarker in psoriasis patients, both for diagnostic purposes and measurement of disease activity during the clinical course. Furthermore, IL-36γ might also provide a future drug target, due to its potential amplifier role in TNFα- and IL-17 pathways in psoriatic skin inflammation. In recent years, different genes and proteins have been highlighted as potential biomarkers for psoriasis, one of the most common inflammatory skin diseases worldwide. However, most of these markers are not psoriasis-specific but also found in other inflammatory disorders. We performed an unsupervised cluster analysis of gene expression profiles in 150 psoriasis patients and other inflammatory skin diseases (atopic dermatitis, lichen planus, contact eczema, and healthy controls). We identified a cluster of IL-17/TNFα-associated genes specifically expressed in psoriasis, among which IL-36γ was the most outstanding marker. In subsequent immunohistological analyses IL-36γ was confirmed to be expressed in psoriasis lesions only. IL-36γ peripheral blood serum levels were found to be closely associated with disease activity, and they decreased after anti-TNFα-treatment. Furthermore, IL-36γ immunohistochemistry was found to be a helpful marker in the histological differential diagnosis between psoriasis and eczema in diagnostically challenging cases. These features highlight IL-36γ as a valuable biomarker in psoriasis patients, both for diagnostic purposes and measurement of disease activity during the clinical course. Furthermore, IL-36γ might also provide a future drug target, due to its potential amplifier role in TNFα- and IL-17 pathways in psoriatic skin inflammation.
Project description:Transcriptional profiling of human mesenchymal stem cells comparing normoxic MSCs cells with hypoxic MSCs cells. Hypoxia may inhibit senescence of MSCs during expansion. Goal was to determine the effects of hypoxia on global MSCs gene expression.