Psoriasis pathology mechanism
Description Summary: Whole-genome expression profiling has been used to characterize molecular-level differences between psoriasis lesions and normal skin.
Pathway analysis, however, is complicated by the fact that expression profiles have been derived from bulk skin biopsies with RNA derived from multiple cell types. We identified differentially expressed genes, including 8 associated with psoriasis susceptibility psoriasis pathology mechanism.
To facilitate pathway analysis, PP versus PN differences in gene expression were analyzed with respect to gene modules, each containing genes with a similar expression pattern in keratinocytes and epidermis. These DEMs were associated with regulatory axes involving cytokines e. We identified an interferon-induced DEM with genes encoding anti-viral proteins designated "STAT"which was activated in psoriatic epidermis but repressed following biologic therapy.
We analyzed a large patient cohort and developed a new approach for delineating epidermis-specific pathways and regulatory mechanisms that underlie altered gene expression in psoriasis.
Our findings highlight previously unrecognized "transcription circuits" that can provide targets for development of non-systemic therapies.