title: 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 twofold) 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 signalling 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 downregulating the expression of Spry2 thus playing important roles in the pathogenesis of psoriasis.
authors.affiliation: Department of Dermatology, Qilu Hospital, Shangdong University, Jinan, Shandong, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Jiang
authors.affiliation: Department of Dermatology, Qilu Hospital, Shangdong University, Jinan, Shandong, China.
authors.forename: Weiyuan
authors.initials: W
authors.lastname: Ma
authors.affiliation: Department of Dermatology, Qilu Hospital, Shangdong University, Jinan, Shandong, China.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Shandong University School of Medicine, Jinan, Shandong, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Jia
authors.affiliation: Shandong University School of Medicine, Jinan, Shandong, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Dermatology, Qilu Hospital, Shangdong University, Jinan, Shandong, China.
authors.forename: Haidong
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Dermatology, Qilu Hospital, Shangdong University, Jinan, Shandong, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Sun
mesh_terms: D020413:3' Untranslated Regions; D049109:Cell Proliferation / Q000235:genetics*; D015536:Down-Regulation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007378:Interleukins / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D015603:Keratinocytes / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011565:Psoriasis / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis*; D015854:Up-Regulation / Q000187:drug effects; D000097043:Interleukin-22
chemical_list: D020413:3' Untranslated Regions; D007378:Interleukins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D035683:MicroRNAs; D012333:RNA, Messenger; D000097043:Interleukin-22; C531907:MIRN122 microRNA, human; C485561:SPRY2 protein, human
keywords: IL-22; Spry2; miR-122-5p; microarray; psoriasis