Table Info

Table 2.

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

Cell source	Cargo	Target cell	Associated molecules and/or signaling pathways	Role in MAFLD	References
Hepatocytes	Not evaluated	KCs	Not evaluated	Pro-inflammatory	[37]
	TRAIL	Bone marrow-derived macrophages (BMDM) and THP-1 macrophages	CHOP-DR5-Caspase-3/Caspase-8-ROCK1 NF-κB RIP1	Promotes M1 polarization of BMDM and THP-1 macrophages	[14]
	ITGβ1	THP-1 macrophages	Not evaluated	Promotes THP-1 inflammatory phenotype and increases THP-1-LSEC adhesion	[38]
	Ceramides	Macrophages	IRE1α-XBP1-Sptlc1 and Sptlc2	Promotes activation and recruitment of macrophages	[11, 39]
	S1P	Macrophages	SphK1 and SphK2 S1P₁ receptor	Promotes activation and recruitment of macrophages	[40]
	mtDNA	KCs and RAW 264.7 cells	TLR-9	Promotes activation of KCs and RAW 264.7 cells	[41, 42]
HSCs	Proteins	Not evaluated	ECM components, proteasome, collagens, vesicular transport, metabolic enzymes, ribosomes, and chaperones	Regulation of HSC activation and fibrogenic pathways in vivo	[43]
HSCs	Fibrogenic proteins	HSCs, macrophages, and endothelial cells (ECs)	PDGF; SHP2; mTOR signaling; ROCK signaling	Autophagy plays a critical role in the release of pro-fibrogenic EVs and HSC function	[44]
LSECs	IGFBP7; ADAMTS1	Fibrotic Th17 cells	Histone deacetylase 2 (HDAC2) DNA methyltransferase 1 (DNMT1)	Epigenetic dysregulation of LSEC exacerbates liver disease	[45]
LSECs	Tropomyosin-1 (TPM1)	Rat hepatocytes, HSCs, human macrophages	ESCRT-dependent pathway (Mvb12-a, Mvb12-b), lipid-rafts structures such as Flot2, tetraspanins CD9 and CD81, and the Rab3 small GTPase	Deactivation of HSCs	[46]

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

Declarations

Author contributions

ZW contributed to the abstract, sections 1, 2, 5.2, conclusions and Figure 1. MX contributed to the Tables 1, 2 and 3, sections 2 and 3. SSS contributed to sections 1 and 2. MCTA contributed to sections 2, 4, and 5.1. MMA contributed to section 4. JAO contributed to section 4.1 and Table 3. JW contributed to section 3.2 and Table 2. MA, SS, LPB, FGvV, HB, and HM contributed to overall lay-out and content of the manuscript. All authors discussed the results and commented on the manuscript.

Conflicts of interest

The authors declare that they have no known competing financial interests of personal relationships that could have appeared to influence the work reported in this research paper.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

This project is financially supported by the China Scholarship Council (CSC) grant 202008320321 (MX), grant 202006250036 (JW) and grant 201806170085 (ZW), Conacyt grant 795389 (MMA), Colciencias International Scholarship Program grant 783-2017 (JAO), the Abel Tasman Talent Program of the University Medical Center Groningen (MCTA), Dutch Digestive Foundation grant WO 21-03 (SSS; HB; HM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Copyright

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