MicroRNA Expression Profiling in Psoriatic Arthritis

Pelosi, Andrea; Lunardi, Claudio; Fiore, Piera Filomena; Tinazzi, Elisa; Patuzzo, Giuseppe; Argentino, Giuseppe; Moretta, Francesca; Puccetti, Antonio; Dolcino, Marzia

doi:10.1155/2018/7305380

Cited by 32 publications

(26 citation statements)

References 39 publications

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“…The upregulation of Th-17 cells related genes and of type I interferon (IFN) inducible genes in PsA patients strengthened the hypothesis that PsA has a strong autoimmune origin, since the coactivity of type I IFN and IL-17 pathways is typical of autoimmunity ( 9 ). Moreover, we confirmed these findings with a miRNA microarray analysis in PBMCs of PsA patients showing that pathway enrichment analysis on gene targets of deregulated microRNAs (miRNAs) revealed signaling pathways typically implicated in PsA, such as TNF, mitogen-activated protein (MAP) kinase, and wingless related integration site (WNT) cascades ( 10 ).…”

Section: Introductionsupporting

confidence: 70%

“…By this study we wanted to provide a more in-depth knowledge on the epigenetic mechanisms that regulate the PsA pathogenesis by analyzing the expression profiles of long non-coding RNAs (lncRNAs) in the same cohort of patients that we studied in our previous work ( 10 ). lncRNAs are important molecules that regulate gene expression through multiple mechanisms and are involved in immune and inflammatory pathways ( 11 ).…”

Section: Introductionmentioning

confidence: 99%

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Long Non-Coding RNAs Play a Role in the Pathogenesis of Psoriatic Arthritis by Regulating MicroRNAs and Genes Involved in Inflammation and Metabolic Syndrome

et al. 2018

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Psoriatic arthritis (PsA) is an inflammatory arthritis, characterized by inflammation of entheses and synovium, leading to joint erosions and new bone formation. It affects 10–30% of patients with psoriasis, and has an estimated prevalence of approximately 1%. PsA is considered to be primarily an autoimmune disease, driven by autoreactive T cells directed against autoantigens present in the skin and in the joints. However, an autoinflammatory origin has recently been proposed. Long noncoding RNAs (lncRNAs) are RNAs more than 200 nucleotides in length that do not encode proteins. LncRNAs play important roles in several biological processes, including chromatin remodeling, transcription control, and post-transcriptional processing. Several studies have shown that lncRNAs are expressed in a stage-specific or lineage-specific manner in immune cells that have a role in the development, activation, and effector functions of immune cells. LncRNAs are thought to play a role in several diseases, including autoimmune disorders. Indeed, a few lncRNAs have been identified in systemic lupus erythematosus, rheumatoid arthritis, and psoriasis. Although several high-throughput studies have been performed to identify lncRNAs, their biological and pathological relevance are still unknown, and most transcriptome studies in autoimmune diseases have only assessed protein-coding transcripts. No data are currently available on lncRNAs in PsA. Therefore, by microarray analysis, we have investigated the expression profiles of more than 50,000 human lncRNAs in blood samples from PsA patients and healthy controls using Human Clariom D Affymetrix chips, suitable to detect rare and low-expressing transcripts otherwise unnoticed by common sequencing methodologies. Network analysis identified lncRNAs targeting highly connected genes in the PsA transcriptome. Such genes are involved in molecular pathways crucial for PsA pathogenesis, including immune response, glycolipid metabolism, bone remodeling, type 1 interferon, wingless related integration site, and tumor necrosis factor signaling. Selected lncRNAs were validated by RT-PCR in an expanded cohort of patients. Moreover, modulated genes belonging to meaningful pathways were validated by RT-PCR in PsA PBMCs and/or by ELISA in PsA sera. The findings indicate that lncRNAs are involved in PsA pathogenesis by regulating both microRNAs and genes and open new avenues for the identification of new biomarkers and therapeutical targets.

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Section: Introductionsupporting

confidence: 70%

Section: Introductionmentioning

confidence: 99%

Long Non-Coding RNAs Play a Role in the Pathogenesis of Psoriatic Arthritis by Regulating MicroRNAs and Genes Involved in Inflammation and Metabolic Syndrome

et al. 2018

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“…AKT2 participates in the PI3K/AKT/mTOR signaling pathway as a critical mediator in psoriasis [49]. SDC2, a target of miR-665 and miR-1207-5p, was found to be upregulated in the blood and lesions of psoriasis patients and to be involved in angiogenesis and the migration and retention of leukocytes [39,50].…”

Section: Discussionmentioning

confidence: 99%

“…Genes targeted by deregulated miRNAs may be significant to psoriasis pathogenesis. Of note, a distinct enrichment of certain pathways was found; for example, pathways relevant to the immune system and proteoglycan metabolism and signaling pathways regulating apoptosis and/or the cell cycle were found [39].…”

Section: Pathway Enrichment Analysis Of Plasma Mirnasmentioning

confidence: 99%

“…The "proteoglycans in cancer" pathway was prominently targeted by deregulated plasma miRNAs of psoriasis patients. Although the pathway is typically associated with many types of cancers, proteoglycans are important in angiogenesis and in the migration and retention of leukocytes [39]. Target genes such as AKT2, WNT1, WNT4, WNT10, WNT11, FGF1, FGF7, FGF9, FGF11, and FGF14 are involved in inflammation, which is a typical feature of psoriasis.…”

Section: Journal Of Immunology Researchmentioning

confidence: 99%

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Plasma MicroRNA Expression Profiles in Psoriasis

Xiao

Liu

Wang

et al. 2020

Journal of Immunology Research

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Background. Psoriasis is an immune-mediated inflammatory chronic skin disease characterized by chronic inflammation in the dermis, parakeratosis, and excessive epidermal growth. MicroRNAs (miRNAs) are key regulators of immune responses. Although differential expression of miRNAs has been reported in certain inflammatory autoimmune diseases, their role in psoriasis has not been fully illuminated. Our aims were to confirm plasma miRNA expression signatures in psoriasis and to examine their potential influence on psoriasis pathogenesis. Methods. A miRNome PCR array was used to analyse the plasma of psoriasis patients and healthy donors. We performed miRNA pathway enrichment and target gene network analyses on psoriasis plasma samples. Results. We found several specific plasma miRNA signatures relevant to psoriasis. The miRNAs targeted pathways associated with psoriasis, such as the VEGF, MAPK, and WNT signaling pathways. Network analysis revealed pivotal deregulated plasma miRNAs and their relevant target genes and pathways regulating psoriasis pathogenesis. Conclusions. This study analysed the expression of plasma miRNAs and their target pathways, elucidating the pathogenesis of psoriasis; these results may be used to design novel therapeutic strategies and to identify diagnostic biomarkers for psoriasis.

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TLR7 endogenous ligands remodel glycolytic macrophages and trigger skin‐to‐joint crosstalk in psoriatic arthritis

et al. 2020

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Thirty percent of psoriasis patients develop psoriatic arthritis (PsA), nevertheless the mechanism remains unknown. Endogenous GU‐rich miRNAs activate endosomal TLR7 that plays a critical role in autoimmune diseases. We found that endogenous TLR7 ligands, miR‐29 and miR‐Let7b, were markedly increased in PsA compared to osteoarthritis (OA) synovial fluid (SF)s. We showed that intradermal (i.d.) miR‐Let7b injection promoted skin inflammation, which was characterized by amplified Th1 cells, CD68+M1 macrophages, and transcriptional upregulation of glycolytic mediators, GLUT1, C‐MYC, and HIF1α. Expansion of skin Th1 cells driven by miR‐Let7b was also linked to elevated M1‐associated IRFs. Interestingly, i.d. miR‐Let7b administration exacerbated suboptimal joint inflammation along with metabolic reconfiguration of the PsA‐like preclinical model. Moreover, TLR7 agonist, R837, potentiated metabolic reprogramming and expression of IL‐1β, IL‐6, and IL‐12 in murine macrophages, enabling myeloid‐to‐T‐cell crosstalk. Consistently, treatment with glycolytic inhibitors, 2‐DG and/or HIF1αi, reversed R837‐induced metabolic remodeling and disrupted the TLR7‐driven inflammatory phenotype in myeloid and lymphoid cells. Similar to miR‐Let7b, R837 also differentiates progenitor cells into mature osteoclasts, primarily through RANKL induction. Taken together, this study indicates that TLR7‐instigated metabolic rewiring of macrophages and their cross‐regulation of T cells connects skin immunopathology to joint inflammation.

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MicroRNA Expression Profiling in Psoriatic Arthritis

Cited by 32 publications

References 39 publications

Long Non-Coding RNAs Play a Role in the Pathogenesis of Psoriatic Arthritis by Regulating MicroRNAs and Genes Involved in Inflammation and Metabolic Syndrome

Long Non-Coding RNAs Play a Role in the Pathogenesis of Psoriatic Arthritis by Regulating MicroRNAs and Genes Involved in Inflammation and Metabolic Syndrome

Plasma MicroRNA Expression Profiles in Psoriasis

TLR7 endogenous ligands remodel glycolytic macrophages and trigger skin‐to‐joint crosstalk in psoriatic arthritis

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