ArticleJournal of hepatology2014
Inhibition of heat shock protein 90 alleviates steatosis and macrophage activation in murine alcoholic liver injury.
Article in Journal of hepatology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 76 citations in OpenAlex.
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- Glutathione contributes to alleviating hepatic injury via host-microbiome interaction and CAR-dependent pathway.Science China. Life sciences · 2025Article
- Role of HSP90 in Type 2 Diabetes Mellitus and Its Association with Liver Diseases.Molecular biotechnology · 2025Review
- Role of macrophage in intervertebral disc degeneration.Bone research · 2025Review
- Emerging role of exosomes during the pathogenesis of viral hepatitis, non-alcoholic steatohepatitis and alcoholic hepatitis.Human cell · 2024Review
- Pathogenesis of Alcohol-Associated Liver Disease.Clinics in liver disease · 2024Review
- Gkongensin A, an HSP90β inhibitor, improves hyperlipidemia, hepatic steatosis, and insulin resistance.Heliyon · 2024Article
- Steroid responsiveness in alcohol-associated hepatitis is linked to glucocorticoid metabolism, mitochondrial repair, and heat shock proteins.Hepatology communications · 2024Article
- Albumosomes formed by cytoplasmic pre-folding albumin maintain mitochondrial homeostasis and inhibit nonalcoholic fatty liver disease.Signal transduction and targeted therapy · 2023Article
- Pathogenic mechanisms and regulatory factors involved in alcoholic liver disease.Journal of translational medicine · 2023Review
- An iron-deficient diet prevents alcohol- or diethylnitrosamine-induced acute hepatotoxicity in mice by inhibiting ferroptosis.Current research in food science · 2022Article
- Impact of preweaning vaccination on host gene expression and antibody titers in healthy beef calves.Frontiers in veterinary science · 2022Article
- Systematic characterization of Puerariae Flos metabolitesFrontiers in pharmacology · 2022Article
- Identifying the Mechanism of Polygoni Cuspidati Rhizoma et Radix in Treating Acute Liver Failure Based on Network Pharmacology and Molecular Docking.Gastroenterology research and practice · 2022Article
- Extracellular Hsp90α, which participates in vascular inflammation, is a novel serum predictor of atherosclerosis in type 2 diabetes.BMJ open diabetes research & care · 2022Observational
- Alcohol-induced Hsp90 acetylation is a novel driver of liver sinusoidal endothelial dysfunction and alcohol-related liver disease.Journal of hepatology · 2021Article
- Hydrogen gas alleviates acute alcohol-induced liver injury by inhibiting JNK activation.Experimental and therapeutic medicine · 2021Article
- Inhibition of heat shock protein 90 alleviates cholestatic liver injury by decreasing IL-1β and IL-18 expression.Experimental and therapeutic medicine · 2021Article
- HSP90 Inhibitor 17-AAG Attenuates Nucleus Pulposus Inflammation and Catabolism Induced by M1-Polarized Macrophages.Frontiers in cell and developmental biology · 2021Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
BACKGROUND &
aimsHeat shock protein 90 (hsp90) is an emerging therapeutic target in chronic liver diseases. Hsp90 plays an important role in liver immune cell activation; however its role in alcoholic liver disease (ALD) remains elusive. Here we hypothesize that hsp90 is crucial in alcohol induced steatosis and pro-inflammatory cytokine production. To test this hypothesis, we employed a pharmacological inhibitor of hsp90, 17-DMAG (17-Dimethylamino-ethylamino-17-demethoxygeldanamycin) in an in vivo mouse model of acute and chronic alcoholic liver injury.
methodsC57BL/6 mice were given either a single dose of ethanol via oral gavage (acute) or chronically fed alcohol for 2 weeks followed by oral gavage (chronic-binge). 17-DMAG was administered during or at the end of feeding. Liver injury parameters, inflammatory cytokines and lipid metabolism genes were analysed.
resultsOur results reveal increased expression of hsp90 in human and mouse alcoholic livers. In vivo inhibition of hsp90, using 17-DMAG, not only prevented but also alleviated alcoholic liver injury, determined by lower serum ALT, AST and reduced hepatic triglycerides. Mechanistic analysis showed that 17-DMAG decreased alcohol mediated oxidative stress, reduced serum endotoxin, decreased inflammatory cells, and diminished sensitization of liver macrophages to LPS, resulting in downregulation of CD14, NFκB inhibition, and decreased pro-inflammatory cytokine production. Hsp90 inhibition decreased fatty acid synthesis genes via reduced nuclear SREBP-1 and favoured fatty acid oxidation genes via PPARα.
conclusionsInhibition of hsp90 decreased alcohol induced steatosis and pro-inflammatory cytokines and inhibited alcoholic liver injury. Hsp90 is therefore relevant in human alcoholic cirrhosis and a promising therapeutic target in ALD.
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