| 研究実績の概要 |
In this research, I have focused on elucidation of the barrier function of the epidermis, with a view to future clinical applications for diseases like AD. To this end, I immunized mice with one round of hapten treatment at the abdomen (day 1), followed by a second round of treatment at the ear (day 7), which led to inflammation two days later (day 9), indicating perturbation of epidermal barrier function by hapten. To reveal the molecular mechanism by which hapten treatment led to disruption of barrier function, I performed RNA-seq using keratinocytes (basal layer) collected from the mouse ear. About 900 genes showed changes in expression patterns upon hapten treatment. Gene ontology (GO) analysis revealed that these genes were associated with immune response such as type I interferon signaling pathway (GO:0060337), cellular response to type I interferon (GO:0071357), and response to interleukin-1 (GO:0070555). Gene expression changes induced by hapten could be mediated by changes in the 3D architecture of the genome, and this possibility was examined by performing Hi-C analysis. Interestingly, upregulated genes moved to an accessible genome compartment (A compartment) upon treatment by hapten, while downregulated genes showed an opposite trend. Taken together, my research indicated that perturbation of the epidermal barrier function is mediated by changes in the 3D conformation of the genome, associated with gene expression changes within those nuclear domains.
|
