IL-22 induced miR-122-5p promotes keratinocyte proliferation by targeting Sprouty2

Abstract

Psoriasis is a common inflammatory skin disease but the exact pathogenesis is largely unknown. Interleukin-22 (IL-22) has demonstrated its vital role in T cell-mediated immune response by interacting with keratinocytes in the pathogenesis of psoriasis. Here, we showed the differentially expressed miRNAs and their potential targets in HaCaT cells stimulated by IL-22 using miRNA and mRNA microarrays. We revealed a total of 20 significantly changed (more than 2-fold) miRNAs in HaCaT cells and validated the results with quantitative reverse transcriptase PCR (qRT-PCR). We demonstrated that miR-122-5p was up regulated both in HaCaT cells stimulated by IL-22 and in psoriatic lesions. Then we aimed to investigate the biological roles and potential mechanism of miR-122-5p in keratinocytes. As a result, CCK-8 assay indicated that overexpression of miR-122-5p in keratinocytes promoted proliferation and conversely inhibition of endogenous miR-122-5p suppressed proliferation. According to the microarray analysis, we assumed that Sprouty2 (Spry2), a negative regulator of extracellular signal regulated kinase/mitogen-activated protein kinase (Erk/MAPK) signaling pathway, was a direct target gene of miR-122-5p. We found that the staining of Spry2 in cytoplasm was mainly localized in both basal and suprabasal layers of epidermis and showed a markedly decreased expression in psoriasis than in normal control by immunohistochemistry. Luciferase reporter and western blot assays in HaCaT cells demonstrated that Spry2 was a direct target gene of miR-122-5p. In conclusion, IL-22 induced miR-122-5p promotes keratinocyte proliferation possibly by down-regulating the expression of Spry2 thus playing important roles in the pathogenesis of psoriasis.

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