| [Background]Psoriasis is a chronic inflammatory skin disease with a strong genetic background.Psoriasis is thought to result from impaired communication between keratinocytes and immune cells,including T cells,dendritic cells,and neutrophils,because of genetic and environm ental factors.Psorias is has a strong genetic component,and genome-wide association studies have identified a growing number of psoriasis susceptibility genes involved in immunity and keratinocyte functions,but little is known about the contribution of specific noncoding RNA genes to psoriasis susceptibility.microRNA(miRNA)is a kind of short noncoding RNA that suppresses the expression of protein-coding gene at the posttranscriptional leve.Each miRNA regulates dozens to hundreds of target genes,which are often functionally related.In patients with psoriasis,early studies identified deregulation of a set of miRNAs in skin lesions.And subsequent work showed that several miRNAs deregulated in patients with psoriasis regulate important keratinocyte and leukocyte functions and contribute to defective keratinocyte/immune cell cross-talk.However,the contribution of genetic variations affecting miRNA function to psoriasis has remained largely unknown.miR-146 a is another miRNA dysregulated in psoriatic lesions mainly involved in the function of immune cells.In innate immune reaction,upregulation of miR-146 a plays a pivotal role in the regulation of inflammation through down-regulation of target gene TNF receptor-associated factor 6(TRAF6)and IL-1 receptor-associated kinase 1(IRAK1),thus the production and effect of cytokine has been lightened.Here we identify an over expression of microRNA-146a(mi R-146a)with psoriasis vulgaris,which obvious in early disease onset in particular.The target gene IRAK1 is a member of IRAKs family,which are a unique family of death domain containing protein kinases that play a key role in the signaling cascades of two receptor families,Toll-like receptors(TLRs)and interleukin-1 receptors(IL-1Rs).Moreover,IRAK1 is served as acritical link modulating the delicate balance between the differentiation of Th17 and Treg cells.It is still unclear the role of miR-146 a dysregulation in psoriasis.[Objective]Therefore,our study has focused on parallel comparisons in lesions of psoriatic patients,and choose the stable keratinocyte cell line HaCaT for research,not only the expression profile of miR-146 a and its impact on the expression of target gene IRAK1 which was supposed to be under the control of miR-146 a,but also the expression of related cytokines.This study explore the pathogenesis of psoriasis which may establish a new and effective way to provide more theoretical support for the improvement of miR-146 a in pathogenesis of psoriasis,and to provide a new strategy for miR-146 a targeted treatment and prognostic analysis of psoriasis.[Methods]1.30 patients with psoriasis vulgaris in observation and 30 healthy subjects in control group were recruited for skin biopsy.RT-qPCR was used to test the mRNA expression of miR-146 a,IRAK1,and the relationship was analysed in psoriasis patients between the relative expression levels mi R-146 a and IRAK1 concentration.Western Blot was performed to explore the protein expression of IRAK1.2.The HaCaT cell model were established.RT-qPCR was used to test the m RNA expression of miR-146 a,IRAK1,Western blot was performed to explore the protein expression of IRAK1 by overexpression and inhibition of miR-146 a.3.The expression levels of IL-23 was detected using Enzyme-linked immunosorbent assay by overexpression and inhibition of mi R-146 a in HaCaT after IL-17 stimulate.[Results]1.The relative expression level of miR-146 a observed in lesions of psoriasis vulgaris patients was significantly higher than that in normal control group(1.96+0.36,0.92+0.14,t=14.05,P<0.01),IRAK1 was significantly higher in lesions of psoriasis vulgaris patients than that in normal control group(2.56+0.42,0.43+0.15,t=39.45,P<0.01);No significantly correlation was observed between the miR-146 a level and IRAK1(r=0.230,P=0.221);Western Blot result showed that IRAK1 protein level increased in lesions of psoriasis vulgaris patients.2.Compared with control group,in the miR-146 a mimics group the expression of miR-146 a in HaCaT cell was greatly increased,the mRNA expression of IRAK1 in HaCaT cell were significantly decreased(P<0.05),and the IRAK1 protein level decreased.However,miR-146 a and IRAK1 mRNA expression and the IRAK1 protein leve was not differ between miR-146 a inhibitor group and control group.3.Compared with control group,the expression of IL-23 was decreased in miR-146 a mimics group,and mimics+IL-17 group,the difference was statistically significant(P <0.05);Compared with control group,the expression of IL-23 was increased in miR-146 a inhibitor group,and mimics+IL-17 group,the difference was statistically significant(P <0.05);[Conclusion]1.The expression of IRAK1 in psoriatic lesions was significantly higher than that in normal skin,suggesting that the abnormal expression of IRAK1 may play an important role in the occurrence and development of psoriasis.2.miR-146 a can inhibit the expression of IRAK1 target gene.3.miR-146 a can significantly reduce the expression of IL-23,miR-146 a may play a negative regulatory role in the inflammatory response.4.miR-146 a may be mediated by IRAK1 expression of inflammatory factors,promote the occurrence and development of psoriasis。... |
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