Curcumin alleviates imiquimod-induced psoriasis in progranulin-knockout mice

Recent advances have revealed that progranulin (PGRN) is related to the aetiology of psoriasis. Moreover, curcumin, a compound derived from turmeric, has been proposed as a potential therapeutic approach in psoriasis-like dermatitis, but it is still unclear whether curcumin affects the development of psoriasis-like skin lesions under PGRN-deficient conditions. Therefore, in this study, we developed a mouse model of psoriatic skin lesions using topical application of imiquimod (IMQ) in both wild type and PGRN-knockout mice to test this possibility. We observed that PGRN deficiency not only increased proinflammatory cytokine IL-17A levels and aggravated psoriasis-like damaged appearance and epidermal thickening but also directly mediated changes in keratinocyte proliferation (Krt 14, cyclinD1 and c-Myc) and differentiation (Krt 10 and Filaggrin) associated gene expression following IMQ challenge, compared to those in the control group. Furthermore, curcumin treatment (50 mg/kg and 200 mg/kg, intragastrically) for 21 consecutive days suppressed the IMQ exposure-induced increase in PGRN expression. Importantly, curcumin treatment significantly alleviated the PGRN deficiency-induced exacerbation of psoriatic appearance, histological features and keratinocyte proliferation after IMQ exposure. In summary, these results demonstrate the direct regulation of PGRN in keratinocyte proliferation and differentiation in psoriatic lesions and demonstrate the protective effect of curcumin on PGRN deficiency-induced psoriatic skin lesion exacerbation.