The pathogenic, therapeutic and diagnostic role of exosomal microRNA in the autoimmune diseases

Mirzaei, Rasoul; Zamani, Farhad; Hajibaba, Marzieh; Rasouli-Saravani, Ashkan; Noroozbeygi, Mina; Gorgani, Melika; Hosseini‐Fard, Seyed Reza; Jalalifar, Saba; Ajdarkosh, Hossein; Abedi, Seyed Hassnan; Keyvani, Hossein; Karampoor, Sajad

doi:10.1016/j.jneuroim.2021.577640

Cited by 72 publications

(55 citation statements)

References 179 publications

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“…Serum and synovial fluid have been very useful in providing information on the preclinical state of patients with RA. Accordingly, we focused our biomarker search on miRNAs packaged in serum-derived exosomes (exomiRNAS), as exomiRNAs have potential as diagnostic disease markers ( 22 ), and because they have the ability to regulate gene expression during disease onset, and are, therefore, good candidates for putative target detection ( 41 ).…”

Section: Discussionmentioning

confidence: 99%

“…Recent evidence has indicated that secreted extracellular vesicles termed “exosomes”, which are involved in intercellular communication by packaging and shuttling various cargo molecules including microRNAs (miRNAs) to recipient cells, may play a critical role in autoimmune-related pathologies ( 20 , 21 ). Moreover, the miRNA cargo of exosomes (exomiRNAs) has potential diagnostic value as biomarkers in several autoimmune diseases ( 22 ). Exosomes and their miRNA cargo have been isolated from different types of bodily fluids in patients with RA ( 23 ).…”

Section: Introductionmentioning

confidence: 99%

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A Serum Biomarker Panel of exomiR-451a, exomiR-25-3p and Soluble TWEAK for Early Diagnosis of Rheumatoid Arthritis

et al. 2021

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BackgroundThe etiology of rheumatoid arthritis (RA) remains poorly understood. Early and accurate diagnosis still difficult to achieve. Inflammatory related molecules released into the circulation such cytokines and exosome-derived microRNAs (exomiRNAs) could be good candidates for early diagnosis of autoimmune diseases. We sought to discover a serum biomarker panel for the early detection of RA based on exomiRNAs and inflammatory markers.MethodsA 179 miRNAs-microarray panel was analyzed in a pilot study (4 early RA and 4 controls). Validation of deregulated exomiRNAs was performed in a larger cohort (24 patients with early RA and 24 controls). miRNet software was used to predict exomiRNA gene-targets interactions. Potentially altered pathways were analyzed by Reactome pathway database search. STRING database was used to predict protein-protein interaction networks. Enzyme-linked immunosorbent assay was used to measure serum levels of sTWEAK and sCD163. Signature biomarker candidates were statistical analyzed.ResultsWe detected 11 differentially expressed exomiRNAs in early RA pilot study. Validation analysis revealed that 6/11 exomiRNAs showed strong agreement with the pilot microarray data (exomiR-144-3p, -25-3p, -15a-5p, -451a, -107 and -185-5p). sTWEAK and sCD163 biomarkers were significantly elevated in the serum of patients with early RA. Receiver operating characteristic (ROC) analysis showed that the best panel to diagnose early RA contained exomiR-451a, exomiR-25-3p and sTWEAK, and could correctly classify 95.6% of patients, with an area under the ROC curve of 0.983 and with 100% specificity and 85.7% sensitivity. The YWHAB gene was identified as a common target of the putative miRNA-regulated pathways.ConclusionA novel serum biomarker panel composed of exomiR-451a, exomiR-25-3p and serum levels of sTWEAK may have use in the early clinical diagnosis of RA. A new predicted exomiRNA-target gene YHWAB has been identified and may have a relevant role in the development of RA.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Serum Biomarker Panel of exomiR-451a, exomiR-25-3p and Soluble TWEAK for Early Diagnosis of Rheumatoid Arthritis

et al. 2021

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“…Obviously, exogenous miR-223 enriched in HMCs-1-derived exosomes inhibits the expression of CLDN8, resulting in the destruction of intestinal barrier function. HMCs-1-derived exosomes and miR-223 may be new therapeutic targets for IBD [97,98].…”

Section: Exosomes From Human Mast Cells-1 (Hmcs-1)mentioning

confidence: 99%

Exosomes as a New Delivery Vehicle in Inflammatory Bowel Disease

Wang

Zhou

et al. 2021

Pharmaceutics

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Inflammatory bowel disease (IBD) is a type of chronic relapsing inflammatory disease. The pathogenesis of IBD is still unclear, which may involve environmental factors, genetic factors, intestinal microbiota disorder, and abnormal immune responses. Exosomes (30–150 nm) are found in various body fluids, including blood, saliva, urine, and cerebrospinal fluid. Exosomes mediate intercellular communication and regulate cell biological activity by carrying non-coding RNAs, proteins, and lipids. There is evidence that exosomes are involved in the pathogenesis of IBD. In view of the important roles of exosomes in the pathogenesis of IBD, this work systematically reviews the latest research progress of exosomes in IBD, especially the roles of exosomes as non-coding RNA delivery systems in the pathogenesis of IBD, including a disordered immune response, barrier function, and intestinal microbiota. The review will help to clarify the pathogenesis of IBD and explore new diagnostic markers and therapeutic targets for patients with IBD.

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“…The distribution of miRNA in exosomes reveals cellular pathophysiology and can alter various biological processes. Increasing data indicate that EVs and their contents, especially miRNAs, affect the pathophysiology of various diseases, including autoimmune diseases (Mirzaei et al, 2021). The EV contents also regulate many signaling pathways (Bahrami et al, 2021).…”

Section: Mesenchymal Stromal Cells and Their Derived Extracellular Vesicles Extracellular Vesicles Are Representative Of Paracrine Effectmentioning

confidence: 99%

Effect of Melatonin for Regulating Mesenchymal Stromal Cells and Derived Extracellular Vesicles

Feng

Yang

Wang

et al. 2021

Front. Cell Dev. Biol.

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Melatonin is a hormone, synthesized in the pineal gland, which primarily controls the circadian rhythm of the body. In recent years, melatonin has also been shown to regulate metabolism, provide neuroprotection, and act as an anti-inflammatory, free radical scavenger. There has also been a recent research interest in the role of melatonin in regulating mesenchymal stromal cells (MSCs). MSCs are pivotal for their ability to differentiate into a variety of different tissues. There is also increasing evidence for the therapeutic prospects of MSCs via paracrine signaling. In addition to secreting cytokines and chemokines, MSCs can secrete extracellular vesicles (EVs), allowing them to respond to injury and promote tissue regeneration. While there has been a major research interest in the use of MSCs for regenerative medicine, the clinical application is limited by many risks, including tumorigenicity, senescence, and sensitivity to toxic environments. The use of MSC-derived EVs for cell-free therapy can potentially avoid the disadvantages of MSCs, which makes this an exciting prospect for regenerative medicine. Prior research has shown that MSCs, via paracrine mechanisms, can identify receptor-independent responses to melatonin and then activate a series of downstream pathways, which exert a variety of effects, including anti-tumor and anti-inflammatory effects. Here we review the synthesis of melatonin, its mechanisms of action, and the effect of melatonin on MSCs via paracrine signaling. Furthermore, we summarize the current clinical applications of melatonin and discuss future prospects.

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The pathogenic, therapeutic and diagnostic role of exosomal microRNA in the autoimmune diseases

Cited by 72 publications

References 179 publications

A Serum Biomarker Panel of exomiR-451a, exomiR-25-3p and Soluble TWEAK for Early Diagnosis of Rheumatoid Arthritis

A Serum Biomarker Panel of exomiR-451a, exomiR-25-3p and Soluble TWEAK for Early Diagnosis of Rheumatoid Arthritis

Exosomes as a New Delivery Vehicle in Inflammatory Bowel Disease

Effect of Melatonin for Regulating Mesenchymal Stromal Cells and Derived Extracellular Vesicles

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