Project description:Atopic dermatitis (AD) is the most common chronic inflammatory skin disorder, characterized by intense itch and recurrent eczematous lesions. Due to lack of proper therapy, the strategies of T cell modulators in combination with targeting keratinocytes and/or myeloid cells might hold promise for achieving disease control in AD patients better than T cell modulators alone. we used microarrays to detail the global programme of gene expression underlying cellularisation and identified distinct classes of up-regulated genes during HY209 treatment in mouse skin
Project description:We identified zinc-alpha-2-glycoprotein (ZAG), a 41-kDa adipokine that regulates body weight, lipid, and mobilization, as a novel biomarker for AD. ZAG levels were consistently decreased in sera, T cells, and skin in human AD patients compared with healthy controls. We used microarrays to obtain the change of signaling molecules by topical treatment of recombinant ZAG using atopic dermatitis induced mouse model.
Project description:Winged bean (WB), Psophocarpus tetragonolobus, is a tropical legume, the potential of which is not yet been understood. We found that a 5 week-oral administration of WB seed extract inhibited wrinkle formation induced by repeated tape stripping (TS), which is a model of lichenification in human chronic eczematous dermatitis. To elucidate mechanism of the effect of WB on this model, we applied microarray analysis. Skin barrier was disrupted by repeated application and removal (tape stripping; TS) of cellophane tape on the dorsal skin of the left side. This procedure was started after 1 week-administration of winged bean (WB) extract, and was conducted 3 times per week for 4 weeks. Dorsal skin samples from three experimental groups were used for microarray experiment. These groups were the non-TS (NT), TS, and TS with oral administration of WB extract (TS/WB). The DNA microarray experiment was performed using Affymetrix Mouse Genome 430 2.0 Array.
Project description:Development of a suitable mouse model would facilitate the investigation of pathomechanisms underlying human psoriasis and would also assist in development of therapeutic treatments. However, while many psoriasis mouse models have been proposed, no single model recapitulates all features of the human disease, and standardized validation criteria for psoriasis mouse models have not been widely applied. In this study, whole-genome transcriptional profiling is used to compare gene expression patterns manifested by human psoriatic skin lesions with those that occur in five psoriasis mouse models (K5-Tie2, imiquimod, K14-AREG, K5-Stat3C and K5-TGFbeta1). While the cutaneous gene expression profiles associated with each mouse phenotype exhibited statistically significant similarity to the expression profile of psoriasis in humans, each model displayed distinctive sets of similarities and differences in comparison to human psoriasis. For all five models, correspondence to the human disease was strong with respect to genes involved in epidermal development and keratinization. Immune and inflammation-associated gene expression, in contrast, was more variable between models as compared to the human disease. These findings support the value of all five models as research tools, each with identifiable areas of convergence to and divergence from the human disease. Additionally, the approach used in this paper provides an objective and quantitative method for evaluation of proposed mouse models of psoriasis, which can be strategically applied in future studies to score strengths of mouse phenotypes relative to specific aspects of human psoriasis. Global transcriptional profiling was utilized to evaluate the similarity between human psoriasis and the psoriasis-like phenotypes that develop in five mouse models (K5-Tie2, IMQ, K14-AREG, K5-Stat3C, K5-TGFbeta1) Expression patterns associated with mouse phenotypes were evaluated by comparing lesional skin from transgenic or IMQ-treated mice (n = 2-3) with normal skin obtained from control mice (n = 2-3).