ArticleCell proliferation2021
EZH2-mediated inhibition of KLF14 expression promotes HSCs activation and liver fibrosis by downregulating PPARγ.
Article in Cell proliferation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 46 citations in OpenAlex.
- Regulatory roles and translational potential of the Kruppel-like factor family in liver disease.iLIVER · 2026Review
- Review
- Histone modifications in skin fibrosis: linking immune dysregulation, metabolic reprogramming, and persistent fibrotic remodeling.Frontiers in immunology · 2026Review
- KLF14 restrained NLRP3-mediated pyroptosis in sepsis-induced acute lung injury by activating DTX3L.Central-European journal of immunology · 2026Article
- Epigenetic reprogramming via EZH2 inhibition rescues fibroadipose pathogenesis in secondary lymphedema through activating PPARγ signaling.Journal of orthopaedic translation · 2025Article
- Adipocyte-specific Krüppel-like factor 14 overexpression confers sex-biased protection from weight gain on a high-fat diet.Physiological reports · 2025Article
- Enhancer of Zeste Homolog 2 Protects Mucosal Melanoma from Ferroptosis via the KLF14-SLC7A11 Signaling Pathway.Cancers · 2024Article
- Noncoding RNA-Mediated Epigenetic Regulation in Hepatic Stellate Cells of Liver Fibrosis.Non-coding RNA · 2024Review
- Altered lipid metabolism promoting cardiac fibrosis is mediated by CD34Experimental & molecular medicine · 2024Article
- Ovarian fibrosis: molecular mechanisms and potential therapeutic targets.Journal of ovarian research · 2024Review
- Enzyme-independent role of EZH2 in regulating cell cycle progression via the SKP2-KIP/CIP pathway.Scientific reports · 2024Article
- Methylation in cornea and corneal diseases: a systematic review.Cell death discovery · 2024Review
- Epigenetic modification in liver fibrosis: Promising therapeutic direction with significant challenges ahead.Acta pharmaceutica Sinica. B · 2024Review
- Exosomes derived from HUVECs alleviate ischemia-reperfusion induced inflammation in neural cells by upregulating KLF14 expression.Frontiers in pharmacology · 2024Article
- Downregulation of Krüppel-like factor 14 accelerated cellular senescence and aging.Aging cell · 2023Article
- Fibrosis-the tale of H3K27 histone methyltransferases and demethylases.Frontiers in cell and developmental biology · 2023Review
- Comprehensive Analysis of Sideroflexin 4 in Hepatocellular Carcinoma by Bioinformatics and Experiments.International journal of medical sciences · 2023Article
- An immune and epigenetics-related scoring model and drug candidate prediction for hepatic carcinogenesis via dynamic network biomarker analysis and connectivity mapping.Computational and structural biotechnology journal · 2023Article
- EZH2 mitigates the cardioprotective effects of mesenchymal stem cell-secreted exosomes against infarction via HMGA2-mediated PI3K/AKT signaling.BMC cardiovascular disorders · 2022Article
- Combined inhibition of PARP and EZH2 for cancer treatment: Current status, opportunities, and challenges.Frontiers in pharmacology · 2022Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
objectivesInduction of deactivation and apoptosis of hepatic stellate cells (HSCs) are principal therapeutic strategies for liver fibrosis. Krüppel-like factor 14 (KLF14) regulates various biological processes, however, roles, mechanisms and implications of KLF14 in liver fibrosis are unknown. MATERIALS AND
methodsKLF14 expression was detected in human, rat and mouse fibrotic models, and its effects on HSCs were assessed. Chromatin immunoprecipitation assays were utilized to investigate the binding of KLF14 to peroxisome proliferator-activated receptor γ (PPARγ) promoter, and the binding of enhancer of zeste homolog 2 (EZH2) to KLF14 promoter. In vivo, KLF14-overexpressing adenovirus was injected via tail vein to thioacetamide (TAA)-treated rats to investigate the role of KLF14 in liver fibrosis progression. EZH2 inhibitor EPZ-6438 was utilized to treat TAA-induced rat liver fibrosis.
resultsKLF14 expression was remarkably decreased in human, rat and mouse fibrotic liver tissues. Overexpression of KLF14 increased LD accumulation, inhibited HSCs activation, proliferation, migration and induced G2/M arrest and apoptosis. Mechanistically, KLF14 transactivated PPARγ promoter activity. Inhibition of PPARγ blocked the suppressive role of KLF14 overexpression in HSCs. Downregulation of KLF14 in activated HSCs was mediated by EZH2-regulated histone H3 lysine 27 trimethylation. Adenovirus-mediated KLF14 overexpression ameliorated TAA-induced rat liver fibrosis in PPARγ-dependent manner. Furthermore, EPZ-6438 dramatically alleviated TAA-induced rat liver fibrosis. Importantly, KLF14 expression was decreased in human with liver fibrosis, which was significantly correlated with EZH2 upregulation and PPARγ downregulation.
conclusionsKLF14 exerts a critical anti-fibrotic role in liver fibrosis, and targeting the EZH2/KLF14/PPARγ axis might be a novel therapeutic strategy for liver fibrosis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.