The Roles of Small Extracellular Vesicles and Small Extracellular Vesicles-derived Non-coding RNA in Non-alcoholic Fatty Liver Disease
Extracellular vesicles(EVs)are a kind of exsomes secreted by cells,which all cells release them as part of their normal physiology and during acquired abnormalities.EVs can be broadly divided into two categories by their sizes,small EVs(sEVs)and medium/large EVs(m/l EVs).As a kind of extracellular vesicle,sEVs are mostly discoid vesicles with diameters ranging from 40 nm to 200 nm.The medium/large EVs are elliptical with a diameter more than 200 nm.sEVs play a crucial role in intercellular communication and have emerged as important mediators in the development and progression of liver diseases.In this review,we discussed the current understanding of the role of sEVs,particularly sEV derived non-coding RNA in non-alcoholic fatty liver disease(NAFLD)and their potential as diagnostic and therapeutic targets.sEVs are small membrane-bound particles secreted by cells,which fuse with plasma membrane and release to extracellular matrix.Depending on the cell of origin,sEVs could contain many cell constituents,including various DNA,RNA,lipids,metabolites,and cytosolic and cell-surface proteins,biomolecules.In addition,many RNA and DNA molecules contained by sEVs,such as mRNA,microRNA(miRNA),long noncoding RNA(lncRNA)and mitochondrial DNA(mtDNA),can be transferred to recipient cells to effectively promote their biological response,physiological and pathological functions.Such sEVs-mediated responses can be disease promoting or restraining.The intrinsic properties of sEVs in regulating complex intracellular pathways has advanced their potential utility in the therapeutic control of many diseases.Recent studies reviewed here also indicate a functional,targeted,mechanism-driven accumulation of specific cellular components in sEVs,suggesting that they have a role in regulating intercellular communication.Many studies have also shown the involvement of sEVs'noncoding RNAs(ncRNAs)in controlling cell activities and their crucial functions in regulating lipid metabolism.sEVs ncRNAs,including miRNAs,lncRNAs,and circular RNAs(circRNAs)regulate physiological functions and maintain lipid metabolism homeostasis.miRNA are small non-coding RNA molecules that regulate posttranscriptional gene expression by repressing messenger RNA-targets.These circulating miRNAs are easily accessible,disease-specific and sensitive to small changes,which makes them ideal biomarkers for diagnostic,prognostic,predictive or monitoring purposes.Specific miRNA signatures can be reflective of disease status and development or indicators of poor treatment response in liver diseases.And lncRNAs have been shown to regulate gene expression by interacting with transcription factors or chromatin-modifying enzymes,which regulate gene expression by binding to target mRNAs.Then circRNAs contributed to NAFLD progression by acting as miRNA sponges,functional protein sponges,or novel templates for protein translation.Finally,sEVs could be engineered to deliver diverse therapeutic payloads,including short interfering RNAs,antisense oligonucleotides and so on,with an ability to direct their delivery to a desired target.The potential of targeting sEVs with lncRNAs and miRNAs not only could be potential diagnostic biomarkers for NAFLD,but also have potential therapeutic effects on NAFLD,which might provide new ideas for the NAFLD treatment.In conclusion,this review provides an overview of the current understanding of the roles of sEVs ncRNAs in NAFLD,so we suggest that further research into sEVs could lead to new diagnostic tools and therapeutic strategies for NAFLD.
small extracellular vesiclesnon-alcoholic fatty liver diseasenon-coding RNAsmicroRNAslong non-coding RNAscircular RNAs
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