Combination of retinoids and narrow-band ultraviolet B inhibits matrix metalloproteinase 13 expression in HaCaT keratinocytes and a mouse model of psoriasis

Abstract

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.

Hidradenitis suppurativa (HS)

“…Since elevated levels of particularly MMP-2, MMP-8, and MMP-9, have been observed in HS lesions, we have chosen to focus on these specific isoforms [74], [75], [118], [119]. Similar trends regarding elevated levels of specific MMPs are observed in psoriasis skin [120]- [123]. MMPs are activated as part of the inflammatory immune response, meaning that these targets are prominent in the later stages of HS.…”

“…Dysregulation and overexpression of MMP-9 seems to be associated with some diseases, thus emphasizing the importance of examining its inhibition and regulation, in relation to HS. Due to the structural similarities between MMP-2 and MMP-9, the inhibition of MMP-9 is also likely to result in the inhibition of MMP-2 and vice versa [123], [129].…”

TAZAROTENE: A Concise Review of Mechanism of Action and Therapeutic Benefits

“…The success rates of treatment and onset of action were greater with larger dose but a decrease in lesions on trunk, limb, knee and elbow was observed with both doses. The response lasted for twelve weeks in 50% of patients after treatment with no reports of tachyphylaxis even after 1 year 41,42 . Xi et al, 2021, found an increased level of MMP13 in the samples of skin lesions and serum from the patients with psoriasis.…”

“…It was approved to be used as cream (0.05 and 0.1%) in US for psoriasis in September 2000, and 0.1% for acne vulgaris in October 2001. 0.1% TZR cream was approved as an adjuvant to other topical retinoids to reduce the signs of facial photodamage in September 2002 42 .…”

“…Prior to TAZORAC therapy, a lack of pregnancy report should be obtained prior to treatment 64 . However, in clinical trials, six women gave birth to healthy infants after TZR treatment during the pregnancy period 42,68 .…”