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GSE65914
Homo sapiens
50 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Rosacea is a common chronic inflammatory skin disease of unknown etiology. Our knowledge about an involvement of the adaptive immune system is very limited. We performed detailed transcriptome analysis, qRT-PCR, and quantitative immunohistochemistry on facial biopsies of rosacea patients, classified according to their clinical subtype. As controls, we used samples from healthy controls. Our study shows significant activation of the immune system in all subtypes of rosacea, characterizing erythematotelangiectatic rosacea (ETR) already as a disease with significant influx of proinflammatory cells. The T cell response is dominated by Th1/Th17-polarized immune cells, as demonstrated by significant upregulation of IFN or IL-17, for example. Chemokine expression patterns support a Th1/Th17 polarization profile of the T cell response. Macrophages and mast cells are increased in all three subtypes of rosacea, while neutrophils reach a maximum in papulopustular rosacea. Our studies also provide evidence for activation of plasma cells with significant antibody production already in ETR, followed by a crescendo pattern towards phymatous rosacea. In sum, Th1/Th17 polarized inflammation and macrophage infiltration is an underestimated hallmark in all subtypes of rosacea. Therapies directly targeting the Th1/Th17 pathway are promising candidates in the future treatment of this skin disease.
Publication Title
Molecular and Morphological Characterization of Inflammatory Infiltrate in Rosacea Reveals Activation of Th1/Th17 Pathways.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 53 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background: Possible outcomes of acne lesions are atrophic scars which may cause serious physical and psychological distress. Current treatments of post-acne scarring remain difficult and often require invasive procedures. Pathophysiological studies on acne scaring investigated only the first week of papule life. Objectives: Study the pathophysiology of atrophic acne scar formation to identify molecular and cellular pathways that can lead to new therapies for the prevention of acne scarring. Methods: Large-scale gene expression profiling of uninvolved acne skin and acne papules of 48 hours and 3 weeks of age, respectively, of both, scar-prone (SP) and non-scar-prone (NSP) patients was performed. Immunohistochemistry techniques were applied to confirm transcriptomics results on the protein and cellular level. Results: Gene expression and immunohistochemistry analyses showed a very similar immune response in 48 hours-old papules in SP and NSP populations characterized by elevated numbers of T cells, neutrophils and macrophages. However, only in SP patients the immune response persisted in 3 week-old papules, and was characterized by an important infiltrate of B cells. Transient down-modulation of genes related to lipid metabolism was observed in 48 hours-old papules in NSP patients, followed by normalization of gene expression levels after 3 weeks. In contrast, in SP patients a drastic reduction of lipid metabolizing enzymes was observed in 3 week-old papules, suggesting irreversible modifications. The affected lipid metabolism genes were found preferentially expressed in human sebaceous glands, pointing to a destruction of sebaceous gland structures after 3 weeks of inflammatory remodelling in SP acne patients.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 48 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Melasma is a commonly acquired hyperpigmentary disorder of the face, but its pathogenesis is poorly understood and its treatment remains challenging. We conducted a comparative histological study on lesional and perilesional normal skin to clarify the histological nature of melasma. Significantly, higher amounts of melanin and of melanogenesis-associated proteins were observed in the epidermis of lesional skin, and the mRNA level of tyrosinase-related protein 1 was higher in lesional skin, indicating regulation at the mRNA level. However, melanocyte numbers were comparable between lesional and perilesional skin. A transcriptomic study was undertaken to identify genes involved in the pathology of melasma. A total of 279 genes were found to be differentially expressed in lesional and perilesional skin. As was expected, the mRNA levels of a number of known melanogenesis-associated genes, such as tyrosinase, were found to be elevated in lesional skin. Bioinformatics analysis revealed that the most lipid metabolism-associated genes were downregulated in lesional skin, and this finding was supported by an impaired barrier function in melasma. Interestingly, a subset of Wnt signaling modulators, including Wnt inhibitory factor 1, secreted frizzled-related protein 2, and Wnt5a, were also found to be upregulated in lesional skin. Immunohistochemistry confirmed the higher expression of these factors in melasma lesions.
Publication Title
Transcriptional profiling shows altered expression of wnt pathway- and lipid metabolism-related genes as well as melanogenesis-related genes in melasma.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 40 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Vitiligo is an acquired depigmentation of the skin inducing a marked alteration of the quality of life of affected individuals. Halting the disease progression and repigmenting the lesional skin represent the two faces of the therapeutic challenge in vitiligo. So far, none of them has been successfully addressed. Oxidative stress and immune system in genetically predisposed individuaLesionalparticipate to the complex pathophysiology of vitiligo. We performed a transcriptome and proteomic analysis on lesional, perilesional and non-depigmented skin of vitiligo patients compared to matched skin controLesionalof healthy subjects. Our results show that the WNT pathway, implicated in melanocytes differentiation, was found to be altered in vitiligo skin. We demonstrated that the oxidative stress decreases WNT expression/activation in keratinocytes and in melanocytes. We developed an ex vivo skin model that remains functional up to 15 days. We then confirmed the decreased activation of the WNT pathway in human skin subjected to oxidative stress. Finally, using pharmacological agents that activate the WNT pathway, we treated the ex vivo depigmented skins from vitiligo patients and successfully induced the differentiation of resident stem celLesionalinto pre-melanocytes supporting further exploration of WNT activators to repigment vitiligo lesions.
Publication Title
Transcriptional Analysis of Vitiligo Skin Reveals the Alteration of WNT Pathway: A Promising Target for Repigmenting Vitiligo Patients.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 34 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Actinic keratoses (AK) are proliferations of pre-neoplastic keratinocytes in the epidermis that are the result of cumulative ultraviolet (UV) radiations from sun exposure. Lesions are commonly found on sites of sun-exposed skin such as the face, balding scalp, and back of the hand. AKs may present on a patient as a few detectable lesions and 5-10% of them are susceptible to transform into SCC. In contrast, Organ Transplant Recipients (OTR) are of increasing risk at developing cancers as a consequence of long-term immunosuppressive therapy. The molecular changes that occur in lesional and perilesional skin of OTR patients 18 weeks following of PDT with topical MAL treatment were investigated to better understand the effect of the therapeutic intervention on the AK lesions. Our data show the complete normalization of the skin biology in the treated areas, i. e restoration of normal proliferation related gene profiles, and correction of aberrantly expressed cancer associated genes. We were also able to uncover a transcriptional signature of a rejuvenation effect induced by MAL-PDT in photodamaged skin opening new avenues in the use of PTD for treating photodamaged skin and field cancerized areas.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The mechanisms of inflammation in acne are not well understood. This study performed in two separate patient populations focused on the activation of adaptive and innate immunity in early inflamed acne. Biopsies were collected from lesional and non-lesional skin of acne patients. Psoriasis patients and healthy volunteers were included in the study for comparison (not included in the records). Using Affymetrix Genechips, we observed significant elevation of the signature cytokines of the Th17 lineage in acne lesions compared to non-lesional skin. The increased expression of IL-17 was confirmed with real-time qPCR (RT-PCR) in two separate patient populations. Cytokines involved in Th17 lineage differentiation (IL-1beta, IL-6, TGF-beta; IL23p19) were remarkably induced at the RNA level. In addition, pro-inflammatory cytokines (IL-8, TNF-), Th1 markers (IL12p40, CXCR3, T-bet, IFN-gamma), T regulatory cell markers (Foxp3, IL-10, TGF-) and antimicrobial peptides (S100A7, S100A9, LNC2, hBD2, hBD3, hCAP18) were induced. Importantly, immunohistochemistry revealed significantly increased numbers of IL-17A positive T cells and CD83 dendritic cells in the acne lesions. In summary our results demonstrate the presence of IL17A positive T cells and the activation of Th17-related cytokines in acne lesions, indicating that the Th17 pathway may play a pivotal role in the disease process, offering new targets of therapy.
Publication Title
IL-17/Th17 pathway is activated in acne lesions.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background: First- and third-generation retinoids are the main treatment in acne. Even though efficacious, they lack full selectivity for RAR expressed in the epidermis and infundibulum. Objectives: To characterize the in vitro metabolism and the pharmacology of the novel retinoid trifarotene. Methods: In vitro assays determined efficacy, potency and selectivity on RARs, as well as the activity on the expression of retinoid target genes in human keratinocytes and ex vivo cultured skin. In vivo studies investigated topical comedolytic, anti-inflammatory and depigmenting properties. The trifarotene-induced gene expression profile was investigated in non-lesional skin of acne patients and compared to ex vivo and in vivo models. Finally, the metabolic stability in human keratinocytes and hepatic microsomes was established. Results: Trifarotene is a selective RAR agonist with >20-fold selectivity over RAR and RAR. Trifarotene is active and stable in keratinocytes but rapidly metabolized by human hepatic microsomes, predicting improved safety. In vivo, trifarotene 0.01% applied topically is highly comedolytic and has antiinflammatory and antipigmenting properties. Gene expression studies indicated potent activation of known retinoid-modulated processes (epidermal differentiation, proliferation, stress response, RA metabolism) and novel pathways (proteolysis, transport/skin hydration, cell adhesion) in ex vivo and in vivo models, as well as in human skin after four weeks of topical application of trifarotene 0.005% cream. Conclusion: Based on its RAR selectivity, rapid degradation in human hepatic microsomes and pharmacological properties including potent modulation of epidermal processes, topical treatment with trifarotene is expected to provide strong efficacy combined with a favourable safety profile in acne and ichthyotic disorders.
Publication Title
Nonclinical and human pharmacology of the potent and selective topical retinoic acid receptor-γ agonist trifarotene.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Analysis of gene expression profiling of human epidermis and sebaceous glands. Skin samples were obtained from 5 healthy individuals undergoing plastic surgery
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 376 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
Whole blood (paxgene) gene expression was measured using Affymetrix microarray from 377 individuals with rheumatoid arthritis.
Publication Title
Integrative genomic deconvolution of rheumatoid arthritis GWAS loci into gene and cell type associations.
Sample Metadata Fields
Sex, Age, Specimen part, Disease
View Samples- Homo sapiens
- 371 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219), Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples