Determination of chemical irritation potential using a defined gene signature set on tissue-engineered human skin equivalents
| Autor: | Amy L. Harding, Helen E. Colley, Robert D. Turner, Sirwan Hadad, Zobaer Hasan, Simon G. Danby, Craig Murdoch, Tetsuo Furuno, Hirofumi Nakanishi |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Co-DEA
cocamide diethanolamine TRPV3 medicine.medical_specialty LDA linear discrimination analysis H2O water Erythema Co-MEA cocamide monoethanolamine HSE human skin equivalent Human skin Dermatology medicine.disease_cause TEER transepithelial electrical resistance LA lactic acid Equivalent medicine CA cinnamaldehyde N-LA neutralized lactic acid PCA principal component analysis MP methylparaben LDH lactate dehydrogenase business.industry CAP capsaicin KC keratinocyte Gene signature MMP matrix metalloproteinase medicine.anatomical_structure HDF human dermal fibroblast CON control RL1-803 Itching Original Article Irritation medicine.symptom Keratinocyte business |
| Zdroj: | JID Innovations JID Innovations, Vol 1, Iss 2, Pp 100011-(2021) |
| ISSN: | 2667-0267 |
| Popis: | There are no physical or visual manifestations that define skin sensitivity or irritation; a subjective diagnosis is made on the basis of the evaluation of clinical presentations, including burning, prickling, erythema, and itching. Adverse skin reaction in response to topically applied products is common and can limit the use of dermatological or cosmetic products. The purpose of this study was to evaluate the use of human skin equivalents based on immortalized skin keratinocytes and evaluate the potential of a 22-gene panel in combination with multivariate analysis to discriminate between chemicals known to act as irritants and those that do not. Test compounds were applied topically to full-thickness human skin equivalent or human ex vivo skin and gene signatures determined for known irritants and nonirritants. Principle component analysis showed the discriminatory potential of the 22-gene panel. Linear discrimination analysis, performed to further refine the gene set for a more high-throughput analysis, identified a putative seven-gene panel (IL-6, PTGS2, ATF3, TRPV3, MAP3K8, HMGB2, and matrix metalloproteinase gene MMP-3) that could distinguish potential irritants from nonirritants. These data offer promise as an in vitro prediction tool, although analysis of a large chemical test set is required to further evaluate the system. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|