Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 전대원 | - |
dc.date.accessioned | 2019-12-10T20:14:35Z | - |
dc.date.available | 2019-12-10T20:14:35Z | - |
dc.date.issued | 2018-12 | - |
dc.identifier.citation | CELL REPORTS, v. 24, no. 11, page. 2985-2999 | en_US |
dc.identifier.issn | 2211-1247 | - |
dc.identifier.uri | https://www.cell.com/cell-reports/fulltext/S2211-1247(18)31186-0?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2211124718311860%3Fshowall%3Dtrue | - |
dc.identifier.uri | https://repository.hanyang.ac.kr/handle/20.500.11754/121155 | - |
dc.description.abstract | Endoplasmic reticulum (ER) stress is associated with liver injury and fibrosis, and yet the hepatic factors that regulate ER stress-mediated inflammasome activation remain unknown. Here, we report that farnesoid X receptor (FXR) activation inhibits ER stress-induced NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome in hepatocytes. In patients with hepatitis B virus (HBV)-associated hepatic failure or non-alcoholic fatty liver disease, and in mice with liver injury, FXR levels in the liver inversely correlated with the extent of NLRP3 inflammasome activation. Fxr deficiency in mice augmented the ability of ER stress to induce NLRP3 and thioredoxin-interacting protein (TXNIP), whereas FXR ligand activation prevented it, ameliorating liver injury. FXR attenuates CCAA-Tenhancer-binding protein homologous protein (CHOP)-dependent NLRP3 overexpression by inhibiting ER stress-mediated protein kinase RNA-like endoplasmic reticulum kinase (PERK) activation. Our findings implicate miR-186 and its target, noncatalytic region of tyrosine kinase adaptor protein 1 (NCK1), in mediating the inhibition of ER stress by FXR. This study provides the insights on how FXR regulation of ER stress ameliorates hepatocyte death and liver injury and on the molecular basis of NLRP3 inflammasome activation. | en_US |
dc.description.sponsorship | This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (Ministry of Science and ICT [MSIP]; NRF-2015R1A2A1A10052663) for S.G.K. and the Basic Science Research Program through NRF funded by the Ministry of Education (2017R1D1A1B03028272) for C.Y.H. The authors thank Dr. Bart Staels (Institut Pasteur de Lille, Lille, France) for providing FXRE luciferase reporter. | en_US |
dc.language.iso | en_US | en_US |
dc.publisher | CELL PRESS | en_US |
dc.subject | THIOREDOXIN-INTERACTING PROTEIN | en_US |
dc.subject | FARNESOID X RECEPTOR | en_US |
dc.subject | ER STRESS | en_US |
dc.subject | CELL-DEATH | en_US |
dc.subject | NONALCOHOLIC STEATOHEPATITIS | en_US |
dc.subject | HEPATIC STEATOSIS | en_US |
dc.subject | OXIDATIVE STRESS | en_US |
dc.subject | DOWN-REGULATION | en_US |
dc.subject | ACTIVATION | en_US |
dc.subject | SURVIVAL | en_US |
dc.title | FXR Inhibits Endoplasmic Reticulum Stress-Induced NLRP3 Inflammasome in Hepatocytes and Ameliorates Liver Injury | en_US |
dc.type | Article | en_US |
dc.relation.no | 11 | - |
dc.relation.volume | 24 | - |
dc.identifier.doi | 10.1016/j.celrep.2018.07.068 | - |
dc.relation.page | 2985-2999 | - |
dc.relation.journal | CELL REPORTS | - |
dc.contributor.googleauthor | Han, Chang Yeob | - |
dc.contributor.googleauthor | Rho, Hyun Soo | - |
dc.contributor.googleauthor | Kim, Ayoung | - |
dc.contributor.googleauthor | Kim, Tae Hyun | - |
dc.contributor.googleauthor | Jang, Kiseok | - |
dc.contributor.googleauthor | Jun, Dae Won | - |
dc.contributor.googleauthor | Kim, Jong Won | - |
dc.contributor.googleauthor | Kim, Bumseok | - |
dc.contributor.googleauthor | Kim, Sang Geon | - |
dc.relation.code | 2018010252 | - |
dc.sector.campus | S | - |
dc.sector.daehak | COLLEGE OF MEDICINE[S] | - |
dc.sector.department | DEPARTMENT OF MEDICINE | - |
dc.identifier.pid | noshin | - |
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