Altered expression of matrix remodelling associated 7 (MXRA7) in psoriatic epidermis: Evidence for a protective role in the psoriasis imiquimod mouse model

摘要

Preliminary data mining performed with Gene Expression Omnibus data sets implied that psoriasis may involve the matrix remodelling associated 7 (MXRA7), a gene with little function information yet. To test that hypothesis, studies were performed in human samples and murine models. Immunohistochemistry in normal human skin showed that MXRA7 proteins were present across the full epidermal layer, with highest expression level detected in the basal layer. In psoriatic samples, MXRA7 proteins were absent in the basal stem cells layer, while suprabasal keratinocytes were stained at a higher level than in normal tissues. In an imiquimod-induced psoriasis-like disease model in mice, diseased skins manifested similar MXRA7 expression pattern and change as in human samples, and MXRA7-deficient mice developed severer psoriasis-like diseases than wild-type mice did. While levels of propsoriatic genes (eg IL17, IL22, IL23) in imiquimod-stimulated MXRA7-deficient mice were higher than in wild-type mice, keratinocytes isolated from MXRA7-deficient mice showed increased proliferation upon differentiation induction in culture. These data demonstrated that MXRA7 gene might function as a negative modulator in psoriasis development when propsoriatic factors attack, presumably via expression alteration or redistribution of MXRA7 proteins in keratinocytes.