Matrix metalloproteinase13 (MMP13) can be released by keratinocytes and fibroblasts and involved in the pathogenesis of skin disorders. Retinoic acid derivative drugs include tazarotene and acitretin. Tazarotene/acitretin and narrow-band ultraviolet B (NB-UVB) irradiation are common treatment options for psoriasis. However, their impact on MMP13 expression in the context of psoriasis has yet to be determined. The expression of MMP13 was analyzed in patients with psoriasis. The effects of tazarotene/acitretin and NB-UVB on MMP13 expression were also investigated in a mouse model of psoriasis. Human HaCaT keratinocytes were exposed to acitretin or NB-UVB and then assayed for cell proliferation and MMP13 expression levels. We showed that patients with psoriasis had increased levels of MMP13 protein in skin lesions and serum samples. Exposure to acitretin and NB-UVB irradiation alone or in combination led to reduction of cell proliferation and MMP13 expression in HaCaT cells. Consistently, tazarotene treatment or NB-UVB irradiation attenuated imiquimod-induced psoriasis-like dermatitis and decreased MMP13 expression in a mouse model. Based on these from HaCaT keratinocytes cells and animal experiments, we suggest that tazarotene/acitretin and NB-UVB irradiation can inhibit the expression of MMP13 in HaCaT keratinocytes and psoriasis mouse models. Blockade of MMP13 activity may have therapeutic potential in improving symptoms of psoriasis.
Matrix metalloproteinase 13 (MMP13) is a zinc-containing endopeptidase secreted by keratinocytes and skin fibroblasts and participates in many inflammatory diseases. Drugs for retinoic acid include tazarotene and acitretin. Tazarotene/acitretin and narrow-band ultraviolet B (NB-UVB) irradiation are used as a general treatment for psoriasis. However, their impact on MMP13 expression has yet to be determined. In this study, we measured the expression of MMP13 in patients with psoriasis, and investigated the effects of tazarotene and/or NB-UVB on MMP13 expression in a mouse model of psoriasis. After exposure to acitretin and/or NB-UVB, immortalized human HaCaT keratinocytes were analyzed for viability and MMP13 expression. Our results showed that MMP13 protein levels increased in skin lesions and serum samples in patients with psoriasis. Treatment with acitretin and NB-UVB irradiation alone or in combination suppressed cell viability and MMP13 expression in HaCaT cells. Consistently, tazarotene treatment and/or NB-UVB irradiation attenuated imiquimod-induced psoriasis-like dermatitis and inhibited MMP13 expression in a mouse model. Taken together, these results indicate that tazarotene/acitretin and NB-UVB irradiation can inhibit the expression of MMP13 in keratinocytes and psoriasis mouse models. Targeting MMP13 may represent a promising therapeutic strategy against psoriasis.
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