Deletion of KLF10 Leads to Stress-Induced Liver Fibrosis upon High Sucrose Feeding
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Lee, Junghoon | - |
dc.contributor.author | Oh, Ah-Reum | - |
dc.contributor.author | Lee, Hui-Young | - |
dc.contributor.author | Moon, Young-Ah | - |
dc.contributor.author | Lee, Ho-Jae | - |
dc.contributor.author | Cha, Ji-Young | - |
dc.date.available | 2021-01-22T07:40:06Z | - |
dc.date.created | 2021-01-20 | - |
dc.date.issued | 2021-01 | - |
dc.identifier.issn | 1661-6596 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/79796 | - |
dc.description.abstract | Liver fibrosis is a consequence of chronic liver injury associated with chronic viral infec-tion, alcohol abuse, and nonalcoholic fatty liver. The evidence from clinical and animal studies indicates that transforming growth factor-β (TGF-β) signaling is associated with the development of liver fibrosis. Krüppel-like factor 10 (KLF10) is a transcription factor that plays a significant role in TGF-β-mediated cell growth, apoptosis, and differentiation. In recent studies, it has been reported to be associated with glucose homeostasis and insulin resistance. In the present study, we investi-gated the role of KLF10 in the progression of liver disease upon a high-sucrose diet (HSD) in mice. Wild type (WT) and Klf10 knockout (KO) mice were fed either a control chow diet or HSD (50% sucrose) for eight weeks. Klf10 KO mice exhibited significant hepatic steatosis, inflammation, and liver injury upon HSD feeding, whereas the WT mice exhibited mild hepatic steatosis with no ap-parent liver injury. The livers of HSD-fed Klf10 KO mice demonstrated significantly increased en-doplasmic reticulum stress, oxidative stress, and proinflammatory cytokines. Klf10 deletion led to the development of sucrose-induced hepatocyte cell death both in vivo and in vitro. Moreover, it significantly increased fibrogenic gene expression and collagen accumulation in the liver. Increased liver fibrosis was accompanied by increased phosphorylation and nuclear localization of Smad3. Here, we demonstrate that HSD-fed mice develop a severe liver injury in the absence of KLF10 due to the hyperactivation of the endoplasmic reticulum stress response and CCAAT/enhance-binding protein homologous protein (CHOP)-mediated apoptosis of hepatocytes. The current study suggests that KLF10 plays a protective role against the progression of hepatic steatosis into liver fibrosis in a lipogenic state. © 2020 by the authors. Licensee MDPI, Basel, Switzerland. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | MDPI AG | - |
dc.relation.isPartOf | International Journal of Molecular Sciences | - |
dc.title | Deletion of KLF10 Leads to Stress-Induced Liver Fibrosis upon High Sucrose Feeding | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 000606072600001 | - |
dc.identifier.doi | 10.3390/ijms22010331 | - |
dc.identifier.bibliographicCitation | International Journal of Molecular Sciences, v.22, no.1, pp.1 - 15 | - |
dc.description.isOpenAccess | N | - |
dc.identifier.scopusid | 2-s2.0-85098849322 | - |
dc.citation.endPage | 15 | - |
dc.citation.startPage | 1 | - |
dc.citation.title | International Journal of Molecular Sciences | - |
dc.citation.volume | 22 | - |
dc.citation.number | 1 | - |
dc.contributor.affiliatedAuthor | Lee, Junghoon | - |
dc.contributor.affiliatedAuthor | Oh, Ah-Reum | - |
dc.contributor.affiliatedAuthor | Lee, Hui-Young | - |
dc.contributor.affiliatedAuthor | Lee, Ho-Jae | - |
dc.contributor.affiliatedAuthor | Cha, Ji-Young | - |
dc.type.docType | Article | - |
dc.subject.keywordAuthor | ER stress | - |
dc.subject.keywordAuthor | Fibrosis | - |
dc.subject.keywordAuthor | Hepatocyte cell death | - |
dc.subject.keywordAuthor | KLF10 | - |
dc.subject.keywordAuthor | NAFLD | - |
dc.subject.keywordAuthor | NASH | - |
dc.subject.keywordAuthor | Smad3 | - |
dc.subject.keywordAuthor | Sucrose diet | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
1342, Seongnam-daero, Sujeong-gu, Seongnam-si, Gyeonggi-do, Republic of Korea(13120)031-750-5114
COPYRIGHT 2020 Gachon University All Rights Reserved.
Certain data included herein are derived from the © Web of Science of Clarivate Analytics. All rights reserved.
You may not copy or re-distribute this material in whole or in part without the prior written consent of Clarivate Analytics.