From:  Extracellular vesicles in metabolic dysfunction associated fatty liver disease: mechanisms, diagnostic and therapeutic implications

Overview of studies demonstrating EV-mediated cell-to-cell communication in the liver in MAFLD

Cell sourceCargoTarget cellAssociated molecules and/or signaling pathwaysRole in MAFLDReferences
HepatocytesNot evaluatedKCsNot evaluatedPro-inflammatory[37]
TRAILBone marrow-derived macrophages (BMDM) and THP-1 macrophagesCHOP-DR5-Caspase-3/Caspase-8-ROCK1
NF-κB
RIP1		Promotes M1 polarization of BMDM and THP-1 macrophages[14]
ITGβ1THP-1 macrophagesNot evaluatedPromotes THP-1 inflammatory phenotype and increases
THP-1-LSEC adhesion		[38]
CeramidesMacrophagesIRE1α-XBP1-Sptlc1 and Sptlc2Promotes activation and recruitment of macrophages[11, 39]
S1PMacrophagesSphK1 and SphK2 S1P1 receptorPromotes activation and recruitment of macrophages[40]
mtDNAKCs and RAW 264.7 cellsTLR-9Promotes activation of KCs and RAW 264.7 cells[41, 42]
HSCsProteinsNot evaluatedECM components, proteasome, collagens, vesicular transport, metabolic enzymes, ribosomes, and chaperonesRegulation of HSC activation and fibrogenic pathways in vivo[43]
Fibrogenic proteinsHSCs, macrophages, and endothelial cells (ECs)PDGF; SHP2; mTOR signaling; ROCK signalingAutophagy plays a critical role in the release of pro-fibrogenic EVs and HSC function[44]
LSECsIGFBP7; ADAMTS1Fibrotic Th17 cellsHistone deacetylase 2 (HDAC2)
DNA methyltransferase 1 (DNMT1)		Epigenetic dysregulation of LSEC exacerbates liver disease[45]
Tropomyosin-1 (TPM1)Rat hepatocytes, HSCs, human macrophagesESCRT-dependent pathway (Mvb12-a, Mvb12-b), lipid-rafts structures such as Flot2, tetraspanins CD9 and CD81, and the Rab3 small GTPaseDeactivation of HSCs[46]
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TRAIL: tumor necrosis factor-related apoptosis-inducing ligand; ITGβ1: integrin β1; IGFBP7: insulin-like growth factor-binding protein-7; Th17: T helper type 17; ROCK1: Rho-associated, coiled-coil-containing protein kinase 1; NF-κB: nuclear factor-κB; RIP1: receptor-interacting protein kinase 1; IRE1α: inositol-requiring transmembrane kinase/endoribonuclease 1α; SphK1: sphingosine kinase 1; TLR-9: Toll-like receptor-9; PDGF: platelet-derived growth factor; SHP2: srchomology-2-domain-containing PTP 2; mTOR: mechanistic target of rapamycin; CHOP: C/EBP homologous protein; DR5: death receptor 5; ADAMTS1: ADAM metallopeptidase with thrombospondin type 1 motif 1; XBP1: X-box binding protein 1; Sptlc1: serine palmitoyltransferase long chain base subunit 1; S1P: sphingosine 1-phosphate; Flot2: flotillin 2; Mvb12-a/b: multivesicular body subunit 12A/B