Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 서원효 | * |
dc.date.accessioned | 2021-08-12T16:30:53Z | - |
dc.date.available | 2021-08-12T16:30:53Z | - |
dc.date.issued | 2021 | * |
dc.identifier.issn | 0021-9738 | * |
dc.identifier.issn | 1558-8238 | * |
dc.identifier.other | OAK-30020 | * |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/258577 | - |
dc.description.abstract | Neutrophil infiltration around lipotoxic hepatocytes is a hallmark of nonalcoholic steatohepatitis (NASH); however, how these 2 types of cells communicate remains obscure. We have previously demonstrated that neutrophil-specific microRNA-223 (miR-223) is elevated in hepatocytes to limit NASH progression in obese mice. Here, we demonstrated that this elevation of miR-223 in hepatocytes was due to preferential uptake of miR-223-enriched extracellular vesicles (EVs) derived from neutrophils as well other types of cells, albeit to a lesser extent. This selective uptake was dependent on the expression of low-density lipoprotein receptor (LDLR) on hepatocytes and apolipoprotein E (APOE) on neutrophil-derived EVs, which was enhanced by free fatty acids. Once internalized by hepatocytes, the EV-derived miR-223 acted to inhibit hepatic inflammatory and fibrogenic gene expression. In the absence of this LDLR- and APOE-dependent uptake of miR-223-enriched EVs, the progression of steatosis to NASH was accelerated. In contrast, augmentation of this transfer by treatment with an inhibitor of proprotein convertase subtilisin/kexin type 9, a drug used to lower blood cholesterol by upregulating LDLR, ameliorated NASH in mice. This specific role of LDLR and APOE in the selective control of miR-223-enriched EV transfer from neutrophils to hepatocytes may serve as a potential therapeutic target for NASH. | * |
dc.language | English | * |
dc.publisher | AMER SOC CLINICAL INVESTIGATION INC | * |
dc.title | Neutrophil-to-hepatocyte communication via LDLR-dependent miR-223-enriched extracellular vesicle transfer ameliorates nonalcoholic steatohepatitis | * |
dc.type | Article | * |
dc.relation.issue | 3 | * |
dc.relation.volume | 131 | * |
dc.relation.index | SCIE | * |
dc.relation.index | SCOPUS | * |
dc.relation.journaltitle | JOURNAL OF CLINICAL INVESTIGATION | * |
dc.identifier.doi | 10.1172/JCI141513 | * |
dc.identifier.wosid | WOS:000620160800003 | * |
dc.author.google | He, Yong | * |
dc.author.google | Rodrigues, Robim M. | * |
dc.author.google | Wang, Xiaolin | * |
dc.author.google | Seo, Wonhyo | * |
dc.author.google | Ma, Jing | * |
dc.author.google | Hwang, Seonghwan | * |
dc.author.google | Fu, Yaojie | * |
dc.author.google | Trojnar, Eszter | * |
dc.author.google | Matyas, Csaba | * |
dc.author.google | Zhao, Suxian | * |
dc.author.google | Ren, Ruixue | * |
dc.author.google | Feng, Dechun | * |
dc.author.google | Pacher, Pal | * |
dc.author.google | Kunos, George | * |
dc.author.google | Gao, Bin | * |
dc.contributor.scopusid | 서원효(56335935100) | * |
dc.date.modifydate | 20240315114146 | * |