Keratinocytes of psoriasis have anti-apoptotic properties including delayed apoptosis process, accelerated proliferation metabolism and postponed differentiation process. However, the specific mechanism leading to the abnormal biological behavior of keratinocytes remains unclear.
We investigated the role of increased RPL22 expression in regulating the abnormal biological behavior of keratinocytes and the mechanism of regulation of RPL22 expression in skin lesions of psoriatic patients.
We examined clinical samples and utilized cytokine-induced cell and IMQ-treated mouse models. We determined the expression and functions of RPL22 in vitro and in vivo.
We showed that RPL22 expression was significantly increased in the skin lesions of psoriasis patients and IMQ-treated psoriatic-like mice. Such increased expression is attributed to hyperacetylation of histone H3K27 in the promoter region of RPL22. Interestingly, overexpression of RPL22 enhanced keratinocyte proliferation by increasing cyclinD1 expression and accelerated CD4+T cells recruitment via upregulating CXCL10 expression. Finally, we demonstrated that RPL22 overexpression promoted psoriasiform phenotypes in IMQ-induced mouse skins.
These findings suggested that RPL22 regulates keratinocytes abnormal biological behavior and contributes to the development of psoriatic phenotypes. Thus, RPL22 might be a novel potential molecular target for treatment of psoriasis.
CXCL10; CyclinD1; H3K27ac; RPL22; keratinocytes; psoriasis.
Copyright © 2021 Zeng, Zhang, Zhang, Zhang, Gao, Tong, Xie, Hu, Chen, Ding and Lu.
Conflict of interest statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Fuentes-Duculan J, Bonifacio KM, Hawkes JE, Kunjravia N, Cueto I, Li X, et al. . Autoantigens ADAMTSL5 and LL37 Are Significantly Upregulated in Active Psoriasis and Localized With Keratinocytes, Dendritic Cells and Other Leukocytes. Exp Dermatol (2017) 26(11):1075–82. 10.1111/exd.13378
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