ArticleCells2020
EX-527 Prevents the Progression of High-Fat Diet-Induced Hepatic Steatosis and Fibrosis by Upregulating SIRT4 in Zucker Rats.
Article in Cells, 2020. 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, 49 citations in OpenAlex.
- Mechanical interplay between adipose tissues and disease progression.Bioengineering & translational medicine · 2026Review
- Pharmacological inhibition of Ubiquitin-Specific Peptidase 10 (USP10) with spautin-1 attenuates adipogenesis through CCAAT/Enhancer-Binding Protein Beta (C/EBPβ) destabilization.Molecular biomedicine · 2025Article
- Contribution of histone deacetylases (HDACs) to the regulation of histone and non-histone proteins: implications for fibrotic diseases.BMB reports · 2025Review
- Sirt4 Overexpression Modulates the JAK2/STAT3 and PI3K/AKT/mTOR Axes to Alleviate Sepsis-Induced Acute Lung Injury.Cell biochemistry and biophysics · 2025Article
- Smad4 deficiency in hepatocytes attenuates NAFLD progression via inhibition of lipogenesis and macrophage polarization.Cell death & disease · 2025Article
- Atrial Cardiomyopathy-associated Arrhythmia and the Impact of Sirtuin Signaling Pathway: A Narrative Review.Current vascular pharmacology · 2025Review
- Therapeutic potential of omaveloxolone in counteracting muscle atrophy post-denervation: a multi-omics approach.Journal of translational medicine · 2024Article
- Contributing roles of mitochondrial dysfunction and hepatocyte apoptosis in liver diseases through oxidative stress, post-translational modifications, inflammation, and intestinal barrier dysfunction.Cellular and molecular life sciences : CMLS · 2024Review
- Tenovin-1, a Selective SIRT1/2 Inhibitor, Attenuates High-fat Diet-induced Hepatic Fibrosis via Inhibition of HSC Activation in ZDF Rats.International journal of biological sciences · 2024Article
- Extracellular matrix remodelling in obesity and metabolic disorders.Life metabolism · 2023Article
- Dendropanoxide Alleviates Thioacetamide-induced Hepatic Fibrosis via Inhibition of ROS Production and Inflammation in BALB/International journal of biological sciences · 2023Article
- The sirtuin family in health and disease.Signal transduction and targeted therapy · 2022Review
- Targeting glutamine metabolism in hepatic stellate cells alleviates liver fibrosis.Cell death & disease · 2022Article
- Tenovin-1 Ameliorates Renal Fibrosis in High-Fat-Diet-Induced Diabetic Nephropathy via Antioxidant and Anti-Inflammatory Pathways.Antioxidants (Basel, Switzerland) · 2022Article
- Progress in Nonalcoholic Fatty Liver Disease: SIRT Family Regulates Mitochondrial Biogenesis.Biomolecules · 2022Review
- Special Issue on "Cellular and Molecular Mechanisms Underlying the Pathogenesis of Hepatic Fibrosis II".Cells · 2022Article
- Pharmacotherapy for Non-Alcoholic Fatty Liver Disease: Emerging Targets and Drug Candidates.Biomedicines · 2022Review
- miRNA-130b-5p promotes hepatic stellate cell activation and the development of liver fibrosis by suppressing SIRT4 expression.Journal of cellular and molecular medicine · 2021Article
- Hypothalamic Actions of SIRT1 and SIRT6 on Energy Balance.International journal of molecular sciences · 2021Review
- Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sirtuin (SIRT) is known to prevent nonalcoholic fatty liver disease (NAFLD); however, the role of SIRT4 in the progression of hepatic fibrosis remains unknown. We hypothesize that EX-527, a selective SIRT1 inhibitor, can inhibit the progression of high-fat diet (HFD)-induced hepatic fibrosis. We found that SIRT4 expression in the liver of NAFLD patients is significantly lower than that in normal subjects. In this study, EX-527 (5 µg/kg), administered to HFD rats twice a week for ten weeks, reduced the serum levels of triglyceride (TG), total cholesterol, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) and attenuated hepatic fibrosis evidenced by Masson's trichrome and hepatic fat by oil red-O staining. EX-527 upregulated SIRT2, SIRT3, and SIRT4 expression in the liver of HFD fed rats but downregulated transforming growth factor-β1 (TGF-β1) and α-smooth muscle actin (α-SMA) expression. It decreased proinflammatory cytokine production and hydroxyproline levels in the serum and SMAD4 expression and restored apoptotic protein (Bcl-2, Bax, and cleaved caspase-3) expression. These data propose a critical role for the SIRT4/SMAD4 axis in hepatic fibrogenesis. SIRT4 upregulation has the potential to counter HFD-induced lipid accumulation, inflammation, and fibrogenesis. We demonstrate that EX-527 is a promising candidate in inhibiting the progression of HFD-induced liver fibrosis.
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Registered trials
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