Contribution of extracellular vesicles to steatosis-related liver disease and their therapeutic potential

Figure 1 Extracellular vesicle biogenesis and molecular cargo. The image shows the release of exosomes and microvesicles from normal, cancer, and apoptotic cells, including their associated molecules. Exosomes from normal cells contain cluster of differentiation (CD) 9, CD63, CD81, and tumor susceptibility gene 101 (TSG101). Arrestin domain-containing protein 1-mediated microvesicles (ARMM) feature arrestin domain containing 1 (ARRDC1). Microvesicles include ADP-ribosylation factor 6 (ARF6) and vesicle-associated membrane protein 3 (VCAMP3). Large oncosomes from cancer cells contain ARF6, Caveolin-1 (Cav-1), and ANNEXIN 1. Apoptotic bodies from apoptotic cells include ARF6, complement component 3b (C3b), thrombospondin (TSP), and phosphatidylserine/ANNEXIN-V. These extracellular vesicles play critical roles in intercellular communication, carrying proteins and nucleic acids that influence recipient cell behavior. MVB: Multivesicular body. Created in BioRender.com.

Figure 2 Exosomes: general molecular cargo. This image shows exosome components and functions. Exosomes contain various nucleic acids [mitochondrial DNA (mtDNA), double-stranded DNA (dsDNA), single-stranded DNA (ssDNA), messenger RNA (mRNA), microRNA (miRNA), long non-coding RNA (lncRNA)], major histocompatibility complex I and II molecules, lipids [leukotriene A4 (LTA4), leukotriene D4 (LTD4), leukotriene C4 (LTC4), prostaglandin E2 (PGE2), phosphatidic acid (PA), lysophosphatidylcholine (LPC)], and tetraspanins [(cluster of differentiation) CD9, CD63, CD81, CD82]. They also include heat shock proteins (HSP90, HSP70, HSP27, HSP60), multivesicular body proteins [tumor susceptibility gene 101 (TSG101), ALG-2 interacting protein X (Alix), vacuolar protein sorting-associated proteins (Vps), Rab proteins], membrane transport proteins [lysosome-associated membrane glycoproteins 1 and 2 (LAMP1 and LAMP2), CD13], signaling proteins (GTPase HRas), cytoskeleton components (actins, tubulins), transcription and synthesis elements (histones, ribosomal proteins), metabolic enzymes [GAPDH, phosphoglycerate kinase (PGK)], trafficking proteins (dynamin, syntaxin-3), anti-apoptosis proteins (ALIX), growth factors [tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta (TGF-B)], death receptors [Fas ligand (FasL)], and iron transport proteins (transferrin receptor). Created in BioRender.com.

Figure 3 Extracellular vesicle protein expression in different chronic liver disease stages. The image illustrates the progression of liver disease from a healthy liver to nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma (HCC). The circular section lists proteins that increase (↑) or decrease (↓) in each stage: In NAFLD, apolipoprotein C-III (APOC3), apolipoprotein C-I (APOC1), prothymosin alpha (PTMA), retinol-binding protein 4 (RBP4), fibulin-1 (FBLN1), and fibulin-3 (FBLN3); in NASH, protein tyrosine phosphatase receptor type G (PTPRG) and C-X-C motif chemokine ligand 10 (CXCL10); in cirrhosis, serpin family C member 1 (SERPINC1) and fibulin-4 (FBLN4); in HCC, hemoglobin subunit alpha 1 (HBA1), fibrinogen gamma chain (FGC), fibrinogen alpha chain (FGA), fibrinogen beta chain (FGB), von Willebrand factor (VWF), CCN family member 2 (CCN2), vesicle-associated membrane protein associated protein A (VAPA), cluster of differentiation (CD) 147, transforming growth factor beta 1 (TGFB1), galectin-3-binding protein (LGALS3BP), haptoglobin (HP), and hemopexin (HPX). Created in BioRender.com.