An Exploration of the Role of MicroRNAs in Psoriasis

Huang, Run‐Yue; Li, Li; Wang, Maojie; Chen, Xiumin; Huang, Qing-Chun; Lu, Chuanjian

doi:10.1097/md.0000000000002030

Cited by 68 publications

(89 citation statements)

References 57 publications

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“…In recent years, with the comprehensive genetic analysis on miR, increasing numbers of specific miR have been discovered to be related with the pathology of psoriasis 19, including miR‐21 20, miR‐146a 21, miR‐424 22 and miR‐99a 23. Other previous studies have also shown that miR‐203, miR‐125b, miR‐99a and miR‐197 were relevant to the pathogenesis of psoriasis by regulating target genes 24, 25, 26, 27.…”

Section: Introductionmentioning

confidence: 99%

Retracted: MicroRNA‐181b negatively regulates the proliferation of human epidermal keratinocytes in psoriasis through targeting TLR4

Feng

Bai

et al. 2016

J Cellular Molecular Medi

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Our study aims to explore the role of microRNA‐181b (miR‐181b) and TLR in the regulation of cell proliferation of human epidermal keratinocytes (HEKs) in psoriasis. Twenty‐eight patients diagnosed with psoriasis vulgaris were selected as a case group with their lesional and non‐lesional skin tissues collected. A control group consisted of 20 patients who underwent plastic surgery with their healthy skin tissues collected. Real‐time quantitative fluorescence polymerase chain reaction (RT‐qPCR), in situ hybridization and immunohistochemistry were used to detect the expressions of miR‐181b and TLR4 in HEKs of healthy skin, psoriatic lesional skin and non‐lesional skin respectively. The 3′ untranslated region (3′UTR) of TLR4 combined with miR‐181b was verified by a dual‐luciferase reporter assay. Western blotting and bromodeoxyuridine were applied for corresponding detection of TLR4 expression and cell mitosis. The expression of miR‐181b in HEKs of psoriatic lesional skin was less than healthy skin and psoriatic non‐lesional skin. In psoriatic lesional and non‐lesional skin, TLR4‐positive cell rates and the number of positive cells per square millimetre were higher than healthy skin. The dual‐luciferase reporter assay verified that miR‐181b targets TLR4. HEKs transfected with miR‐181b mimics had decreased expression of TLR4, along with the decrease of mitotic indexes and Brdu labelling indexes. However, HEKs transfected with miR‐181b inhibitors showed increased TLR4 expression, mitotic indexes and Brdu labelling indexes. HEKs transfected with both miR‐181b inhibitors and siTLR4 had decreased mitotic indexes and Brdu labelling indexes. These results indicate that miR‐181b can negatively regulate the proliferation of HEKs in psoriasis by targeting TLR4.

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Section: Introductionmentioning

confidence: 99%

Retracted: MicroRNA‐181b negatively regulates the proliferation of human epidermal keratinocytes in psoriasis through targeting TLR4

Feng

Bai

et al. 2016

J Cellular Molecular Medi

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“…It is tempting to speculate that aberrant epigenetic silencing of the miR-197 promoter underlies its decreased expression in psoriasis. The mechanism leading to miR-197 silencing, as well to additional alterations in miRNAs in the psoriatic lesion [25,26,50,51], should be further investigated. Study of the epigenetic structure of miR-197 and its putative promoter sequences in the psoriatic genome might partially answer this question.…”

Section: Discussionmentioning

confidence: 99%

Positive-Negative Feedback Loop between Mir-197 and IL-17A Signaling in Human Keratinocytes

Elharrar¹,

Masalha²,

Lerman³

et al. 2016

Immunome Res

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Psoriasis is a chronic inflammatory skin disorder which results from pathological interactions between activated immunocytes and keratinocytes. Recent studies implicated the role of IL-17 and IL-22, secreted from Th17 and Th22 in the generation and propagation of the psoriatic plaque. Previously, we and others have shown that the expression of miR-197 is significantly decreased in psoriatic lesions. We further showed that miR-197 targets IL-22RA1 and that ectopic expression of miR-197 prevent IL-22 induced proliferation and migration of keratinocytes.Since the 3'UTR of the IL17RA subunit mRNA contains a putative binding site for miR-197, our aim was to expand our understanding of the miRNA-mediated crosstalk between immunocytes and keratinocytes by studying the effect of miR-197 expression on IL-17A signaling pathway. Luciferase reporter assays along with Western blot analysis revealed that miR-197 directly targets the 3'UTR of IL17RA. Furthermore, ectopic expression of miR-197 led to a significant decrease in IL-17A-induced expression of CCL20, a known downstream effector of IL-17A. Interestingly, the addition of IL-17A to keratinocytes led to a rapid and transient increase in the expression of miR-197. Chromatin immuno-precipitation assays showed that keratinocytes' treatment with IL-17 leads to C/EBP binding to the promoter region of miR-197, and that the expression level of miR-197 is directly proportional to the extent of C/EBP binding to the promoter. Moreover, following treatment with IL-17A, the histone acetylation pattern at the miR-197 promoter turns to become characteristic of transcribed chromatin.Taken together, our results suggest that a positive-negative feedback loop exists between IL-17A and miR-197 in keratinocytes; the cytokine induces the binding of C/EBPα to miR-197 promoter sequences, enhances miR-197 expression that negatively attenuates IL-17 receptor and decreases the input along the IL-17A pathway. Our work suggests that in psoriasis, decreased expression of miR-197 may prevent the miR-197-induced attenuation of the IL-17 cascade, leading to its over-activity.

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“…These studies have shown that epigenetic modifications are associated with a variety of diseases, e.g. IBD78, multiple sclerosis9, psoriasis10 and systemic lupus erythematosus11. The molecular basis of epigenetic regulation is complex.…”

mentioning

confidence: 99%

Doxycycline, metronidazole and isotretinoin: Do they modify microRNA/mRNA expression profiles and function in murine T-cells?

Becker

Bengs

Aluri³

et al. 2016

Sci Rep

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1Inflammatory bowel disease (IBD) may develop due to an inflammatory response to commensal gut microbiota triggered by environmental factors in a genetically susceptible host. Isotretinoin (acne therapy) has been inconsistently associated with IBD onset and flares but prior treatment with antibiotics, also associated with IBD development, complicates the confirmation of this association. Here we studied in mice whether doxycycline, metronidazole or isotretinoin induce epigenetic modifications, and consequently change T-cell mRNA expression and/or function directly after treatment and after a 4 week recovery period. Isotretinoin induced IL-10 signaling in Tregs and naive T-cells directly after treatment and reduced effector T-cell proliferation alone and in co-culture with Tregs. Metronidazole activated processes associated with anti-inflammatory pathways in both T-cell subsets directly after the treatment period whereas doxycycline induced an immediate proinflammatory expression profile that resolved after the recovery period. Long-term changes indicated an inhibition of proliferation by doxycycline and induction of beneficial immune and metabolic pathways by metronidazole. Persistent alterations in microRNA and mRNA expression profiles after the recovery period indicate that all three medications may induce long-term epigenetic modifications in both T-cell subsets. Yet, our data do not support the induction of a long-term pro-inflammatory phenotype in murine Tregs and naive T-cells.Inflammatory bowel diseases (IBD) with the two main forms, Crohn's disease (CD) and ulcerative colitis (UC), are chronic and relapsing inflammatory conditions of the gastrointestinal tract that affect an increasing number of patients worldwide 1 . The precise pathogenesis of IBD is multifactorial and is not completely elucidated yet. It is generally considered that environmental factors represent an important contributor to the pathogenesis of IBD by triggering an inappropriate and progressive immune response to the commensal gut microbiota in a genetically predisposed host 2 . To date, genome-wide association studies have identified more than 240 IBD susceptibility loci, affecting genes involved in immune regulation, mucosal immune response, autophagy and epithelial barrier function [3][4][5] . Currently available data support the concept that IBD is a polygenic disease and suggest that non-genetic modifications involved in regulatory processes might have an impact on susceptibility and severity of disease 6 . Mechanisms of gene regulation that do not alter the basic sequence of DNA are called epigenetic regulations and have been studied extensively over the last few years. These studies have shown that epigenetic modifications are associated with a variety of diseases, e.g. IBD 7,8 , multiple sclerosis 9 , psoriasis 10 and systemic lupus erythematosus 11. The molecular basis of epigenetic regulation is complex. Importantly, changes may remain through cell division, and last for many generations (long-term effects) 12 . So far, th...

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An Exploration of the Role of MicroRNAs in Psoriasis

Cited by 68 publications

References 57 publications

Retracted: MicroRNA‐181b negatively regulates the proliferation of human epidermal keratinocytes in psoriasis through targeting TLR4

Retracted: MicroRNA‐181b negatively regulates the proliferation of human epidermal keratinocytes in psoriasis through targeting TLR4

Positive-Negative Feedback Loop between Mir-197 and IL-17A Signaling in Human Keratinocytes

Doxycycline, metronidazole and isotretinoin: Do they modify microRNA/mRNA expression profiles and function in murine T-cells?

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