BACKGROUND_AIMS: Hepatic stellate cells (HSCs) play a key role in @entity1575 in various chronic @entity409 including @entity1561 ( @entity1561 ). The development of @entity1575 requires a phenotypic switch from quiescent to activated HSCs. The triggers for HSCs activation in @entity1561 remain poorly understood. We investigated the role and molecular mechanism of extracellular vesicles (EVs) released by hepatocytes during lipotoxicity in modulation of HSC phenotype. METHODS: EVs were isolated from fat-laden hepatocytes by differential centrifugation and incubated with HSCs. EV internalization and HSCs activation, migration and proliferation were assessed. Loss- and gain-of-functions studies were performed to explore the potential role of @entity5601 -y-targeting miRNAs carried by EVs into HSC. RESULTS: Hepatocyte-derived EVs released during lipotoxicity are efficiently internalized by HSCs resulting in their activation, as shown by marked up-regulation of pro-fibrogenic genes ( @entity1970 and @entity1552 ), proliferation, @entity6722 and wound healing responses. These changes were associated with miRNAs shuttled by EVs and suppression of @entity5601 -y expression in HSC. Hepatocyte-derived EVs miRNA content included various miRNAs that are known inhibitors of @entity5601 -y expression with miR-128-3p being the most effectively transferred. Furthermore loss- and gain-of-function studies identified miR-128-3p as a central modulator of the effects of EVs on @entity5601 -y inhibition and HSC activation. CONCLUSION: Our findings demonstrate a link between fat-laden hepatocyte-derived EVs and @entity1575 and have potential implications for the development of novel anti-fibrotic targets for @entity1561 and other @entity66 .

Lipid-induced hepatocyte-derived extracellular vesicles regulate hepatic stellate cell via microRNAs targeting XXXX -y.

@entity1552 :: ('7077', 'Gene') :: ['TIMP-2'] @entity6722 :: ('MESH:C565534', 'Disease') :: ['chemotaxis'] @entity66 :: ('MESH:D004194', 'Disease') :: ['fibrotic diseases'] @entity409 :: ('MESH:D008107', 'Disease') :: ['liver disorders'] @entity1970 :: ('58', 'Gene') :: ['Collagen-I, a-SMA'] @entity1561 :: ('MESH:D065626', 'Disease') :: ['NAFLD', 'nonalcoholic fatty liver disease'] @entity5601 :: ('5465', 'Gene') :: ['PPAR'] @entity1575 :: ('MESH:D008103', 'Disease') :: ['liver fibrosis']
@entity5601 :: (5465,Gene) :: ['PPAR']
