{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T17:50:36Z","timestamp":1789667436617,"version":"4.0.1"},"reference-count":58,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,12,30]],"date-time":"2020-12-30T00:00:00Z","timestamp":1609286400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2019R1A2C2006001"],"award-info":[{"award-number":["NRF-2019R1A2C2006001"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2016R1D1A1B 03935001"],"award-info":[{"award-number":["NRF-2016R1D1A1B 03935001"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","award":["HI14C1135"],"award-info":[{"award-number":["HI14C1135"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Korea Mouse Phenotyping Project","award":["2013M3A9D5072550"],"award-info":[{"award-number":["2013M3A9D5072550"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Liver fibrosis is a consequence of chronic liver injury associated with chronic viral infection, alcohol abuse, and nonalcoholic fatty liver. The evidence from clinical and animal studies indicates that transforming growth factor-\u03b2 (TGF-\u03b2) signaling is associated with the development of liver fibrosis. Kr\u00fcppel-like factor 10 (KLF10) is a transcription factor that plays a significant role in TGF-\u03b2-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 investigated 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 apparent liver injury. The livers of HSD-fed Klf10 KO mice demonstrated significantly increased endoplasmic 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.<\/jats:p>","DOI":"10.3390\/ijms22010331","type":"journal-article","created":{"date-parts":[[2020,12,30]],"date-time":"2020-12-30T20:13:41Z","timestamp":1609359221000},"page":"331","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Deletion of KLF10 Leads to Stress-Induced Liver Fibrosis upon High Sucrose Feeding"],"prefix":"10.3390","volume":"22","author":[{"given":"Junghoon","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Lee Gil Ya Cancer and Diabetes Institute, Gachon University College of Medicine, Incheon 21999, Korea"},{"name":"Department of Health Sciences and Technology, GAIHST, Gachon University, Incheon 21999, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ah-Reum","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Lee Gil Ya Cancer and Diabetes Institute, Gachon University College of Medicine, Incheon 21999, Korea"},{"name":"Department of Health Sciences and Technology, GAIHST, Gachon University, Incheon 21999, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3464-6382","authenticated-orcid":false,"given":"Hui-Young","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Lee Gil Ya Cancer and Diabetes Institute, Gachon University College of Medicine, Incheon 21999, Korea"},{"name":"Department of Health Sciences and Technology, GAIHST, Gachon University, Incheon 21999, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young-Ah","family":"Moon","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Inha University School of Medicine, Incheon 22212, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2170-355X","authenticated-orcid":false,"given":"Ho-Jae","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Lee Gil Ya Cancer and Diabetes Institute, Gachon University College of Medicine, Incheon 21999, Korea"},{"name":"Department of Health Sciences and Technology, GAIHST, Gachon University, Incheon 21999, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8557-6214","authenticated-orcid":false,"given":"Ji-Young","family":"Cha","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Lee Gil Ya Cancer and Diabetes Institute, Gachon University College of Medicine, Incheon 21999, Korea"},{"name":"Department of Health Sciences and Technology, GAIHST, Gachon University, Incheon 21999, Korea"},{"name":"Gachon Medical Research Institute, Gachon University Gil Medical Center, Incheon 21565, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1053\/j.gastro.2005.04.014","article-title":"The natural history of nonalcoholic fatty liver disease: A population-based cohort study","volume":"129","author":"Adams","year":"2005","journal-title":"Gastroenterology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1111\/j.1365-2036.2007.03246.x","article-title":"Gi epidemiology: Nonalcoholic fatty liver disease","volume":"25","author":"Angulo","year":"2007","journal-title":"Aliment. 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