Psoriasis is a chronic inflammatory disease, affecting more than millions of people in the world. Recently, the mTOR inhibitor rapamycin (RAPA) was reported to be involved in the pathogenesis of psoriasis. However, the underlying mechanism remains unclear. Haematoxylin and eosin staining was used to examine the effects of RAPA on inflammatory level of lesional tissues from patients with psoriasis and animal models. Quantitative real-time PCR, immunohistochemistry and western blot assay were performed to assess the effects of RAPA on tropomyosins (TPMs) expression in patients with psoriasis, cell models and animal models. Phalloidin staining was used to assess the RAPA effects on cell skeleton. The effects of RAPA on cell proliferation and cell cycle were detected by CCK-8 assay, EdU staining and flow cytometry. Methylation status of TPMs was analysed by methylation-specific PCR. The expression of TPM1 and TPM2 was significantly downregulated, while their methylation level was obviously higher in the lesional tissues, cell models and animal models of psoriasis. After treated with RAPA, the expression and methylation levels of TPMs were all restored in the cell models and animal models of psoriasis. RAPA inhibited cell proliferation and decreased the ratio of S phase cell in Hacat or human epidermal keratinocytes cell models of psoriasis. Finally, the activated ERK1/2 and mTOR pathways in the cell model and animal model of psoriasis were suppressed by the treatment of RAPA. RAPA could be used as an effective agent for the treatment of psoriasis by decreasing the methylation level of TPM1 and TPM2 via inhibiting the ERK1/2 and mTOR signalling pathways.
Keywords: DNA methylation; Psoriasis; TNF-α; rapamycin; tropomyosin.
© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.