preview

Extracellular Vesimona Essay

Better Essays

EVs as Pathogenic Mediators in NASH Cells release diverse types of membrane-bound extracellular vesicles into the extracellular milieu. These can be further classified into three main subgroups based on their cellular biogenesis: exosomes, microvesicles, and apoptotic bodies.21 Exosomes (~50-100 nm diameter) originate from the multivesicular body (MVB); MVBs are well-characterized endosomal precursors of the lysosomal degradation pathway. MVBs can also fuse with the plasma membrane. In this case, their intraluminal vesicle contents are released into the extracellular space; thus becoming “exosomes”.22 Microvesicles (~50-1000 nm diameter) bud directly from the plasma membrane. Apoptotic bodies (more than 500 nm in diameter) represent …show more content…

One of the early reports of their role in an animal model of NASH was the observation that adoptive transfer of EVs isolated from the serum of high fat diet-fed mice into chow diet-fed mice results in immature myeloid cells activation and homing to the liver, which was associated with increased levels of hepatic proinflammatory markers and serum aminotransferases.32 Subsequent reports demonstrated a significant increase in the release of EVs from hepatocytes upon treatment with lipids such as palmitate and its active metabolite lysophosphatidylcholine (LPC),27 28 33 toxic lipid-induced EV release by hepatocytes was observed across different species.28 EVs derived from hepatocyte under lipotoxic stress are heterogeneous regarding their biogenesis, selected cargo, release, and intended target cells. For example, LPC-induced EV release is mediated by the stress kinase mixed lineage kinase 3 (MLK3).33 Furthermore, MLK3 regulates the chemotactic cargo of the EVs. Genetic or pharmacological inhibition of MLK3 results in a reduced abundance of the potent C-X-C motif chemokine ligand 10 (CXCL10) in vesicles derived from LPC-treated hepatocytes.33 Likewise, MLK3-/- mice fed a NASH-inducing diet34 have reduced CXCL10 levels in their plasma EVs. This, in turn, is

Get Access