Mir214-3p and Hnf4a/Hnf4α reciprocally regulate Ulk1 expression and autophagy in nonalcoholic hepatic steatosis
DC Field | Value | Language |
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dc.contributor.author | Lee, Da-Hye | - |
dc.contributor.author | Park, So-Hyun | - |
dc.contributor.author | Ahn, Jiyun | - |
dc.contributor.author | Hong, Seung Pyo | - |
dc.contributor.author | Lee, Eunyoung | - |
dc.contributor.author | Jang, Young-Jin | - |
dc.contributor.author | Ha, Tae-Youl | - |
dc.contributor.author | Huh, Yang Hoon | - |
dc.contributor.author | Ha, Seung-Yeon | - |
dc.contributor.author | Jeon, Tae-Il | - |
dc.contributor.author | Jung, Chang Hwa | - |
dc.date.accessioned | 2021-10-16T03:40:08Z | - |
dc.date.available | 2021-10-16T03:40:08Z | - |
dc.date.created | 2020-10-26 | - |
dc.date.issued | 2021-09 | - |
dc.identifier.issn | 1554-8627 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/82388 | - |
dc.description.abstract | Macroautophagy/autophagy, a self-degradative process, regulates metabolic homeostasis in response to various stress conditions and is a therapeutic target for nonalcoholic fatty liver disease. We found that autophagic activity was inhibited as a result of a significant reduction in the expression of autophagy-related genes such as Ulk1 in a mouse model and patients with fatty liver. This downregulation was caused by increased Mir214-3p levels and decreased Hnf4a/Hnf4α mRNA levels in hepatocytes. Mir214-3p suppressed Ulk1 expression through direct binding at a 3′ untranslated region sequence. Hnf4a directly activated transcription of Ulk1. We investigated lipid accumulation and the expression of autophagy-related genes in the livers of mice treated with anti-Mir214-3p. Hepatic steatosis was alleviated, and Ulk1 mRNA levels were significantly increased by locked nucleic acid-mediated Mir214-3p silencing. Additionally, autophagosome formation and MAP1LC3/LC3-II protein levels were increased, indicating an increase in autophagic activity. Interestingly, suppression of Mir214-3p did not ameliorate fatty liver under Ulk1 suppression, suggesting that reduced Mir214-3p levels mitigate hepatic steatosis through upregulation of Ulk1. These results demonstrate that inhibition of Mir214-3p expression ameliorated fatty liver disease through increased autophagic activity by increasing the expression of Ulk1. Thus, Mir214-3p is a potential therapeutic target for nonalcoholic fatty disease. Abbreviations: AMPK: adenosine monophosphate-activated protein kinase; ATG: autophagy-related; ChIP: chromatin immunoprecipitation; CTSB: cathepsin B; CTSL: cathepsin L; CQ: chloroquine; HFD: high-fat diet; HNF4A: hepatocyte nuclear factor 4, alpha; IF: immunofluorescence; IHC: immunohistochemistry; LDs: lipid droplets; Leup: leupeptin; LFD: low-fat diet; LNA: locked nucleic acid; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; miRNA: microRNA; MTOR: mechanistic target of rapamycin kinase; NAFLD: non-alcoholic fatty liver disease; NASH: non-alcoholic steatohepatitis; PCR: polymerase chain reaction; TEM: transmission electron microscopy; TF: transcription factor; TLDA: TaqMan low-density array; ULK1: unc-51 like kinase 1; UTR: untranslated region. © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | TAYLOR & FRANCIS INC | - |
dc.relation.isPartOf | Autophagy | - |
dc.title | Mir214-3p and Hnf4a/Hnf4α reciprocally regulate Ulk1 expression and autophagy in nonalcoholic hepatic steatosis | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 000579684600001 | - |
dc.identifier.doi | 10.1080/15548627.2020.1827779 | - |
dc.identifier.bibliographicCitation | Autophagy, v.17, no.9, pp.2415 - 2431 | - |
dc.description.isOpenAccess | N | - |
dc.identifier.scopusid | 2-s2.0-85092766412 | - |
dc.citation.endPage | 2431 | - |
dc.citation.startPage | 2415 | - |
dc.citation.title | Autophagy | - |
dc.citation.volume | 17 | - |
dc.citation.number | 9 | - |
dc.contributor.affiliatedAuthor | Ha, Seung-Yeon | - |
dc.type.docType | Article | - |
dc.subject.keywordAuthor | autophagosome | - |
dc.subject.keywordAuthor | high-fat diet | - |
dc.subject.keywordAuthor | lysosome | - |
dc.subject.keywordAuthor | microRNA | - |
dc.subject.keywordAuthor | nonalcoholic fatty liver disease | - |
dc.subject.keywordAuthor | transcription factor | - |
dc.subject.keywordPlus | FATTY LIVER-DISEASE | - |
dc.subject.keywordPlus | TRANSCRIPTIONAL REGULATION | - |
dc.subject.keywordPlus | MICRORNA BIOGENESIS | - |
dc.subject.keywordPlus | GENE-EXPRESSION | - |
dc.subject.keywordPlus | INHIBITION | - |
dc.subject.keywordPlus | DEFICIENCY | - |
dc.subject.keywordPlus | SYSTEM | - |
dc.subject.keywordPlus | TARGET | - |
dc.subject.keywordPlus | TFEB | - |
dc.relation.journalResearchArea | Cell Biology | - |
dc.relation.journalWebOfScienceCategory | Cell Biology | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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