ArticleInternational journal of molecular sciences2023
Hepatic NLRP3-Derived Hsp70 Binding to TLR4 Mediates MASLD to MASH Progression upon Inhibition of PP2A by Harmful Algal Bloom Toxin Microcystin, a Second Hit.
Article in International journal of molecular sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 11 citations in OpenAlex.
- Pooled it
- Metabolic dysfunction-associated steatotic liver disease: pathogenic mechanisms and exercise-induced molecular adaptations.Lipids in health and disease · 2026Review
- Flavonoids for MASLD: Hepatic Lipid Targets, Biopharmaceutic Barriers, and Formulation Strategies.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Targeting Mitochondria in MASLD: Comparative Evaluation of MitoQ and SS-31 (Elamipretide) in Aged Female Mice under Nutritional Stress.Physiological research · 2026Article
- Total Flavonoids ofNutrients · 2026Article
- Rebamipide Reprograms Hepatic Networks to Prevent and Reverse Metabolic-Dysfunction-Associated Steatotic Liver Disease: Multi-Omics Insights and Histological Validation.Pharmaceuticals (Basel, Switzerland) · 2026Article
- The bidirectional relationship between diabetes mellitus and liver disease: Mechanisms, clinical implications, and management strategies.Endocrine · 2026Review
- Remnant cholesterol inflammatory index and MASLD in U.S. adults: mediation role of triglyceride-glucose index.Journal of clinical & translational endocrinology · 2026Article
- Immune Determinants of MASLD Progression: From Immunometabolic Reprogramming to Fibrotic Transformation.Biology · 2026Review
- Development and validation of a novel metabolic-inflammatory health-related nomogram for predicting in-hospital mortality in older patients with type 2 diabetes mellitus combined with cardiovascular disease.Frontiers in medicine · 2026Article
- MASLD: Lipotoxicity and Imaging Parallels from Liver Steatosis to Kidney Injury.Life (Basel, Switzerland) · 2025Review
- Lysozyme and dandelion extract alleviate tearing eye disease by reducing inflammation and oxidative stress through canine corneal fibroblast model established.Veterinary research communications · 2025Article
- Green tea epigallocatechin gallate attenuate metabolic dysfunction-associated steatotic liver disease by regulation of pyroptosis.Lipids in health and disease · 2025Article
- Metabolic-Dysfunction-Associated Steatotic Liver Disease: Molecular Mechanisms, Clinical Implications, and Emerging Therapeutic Strategies.International journal of molecular sciences · 2025Review
- Heat shock proteins (HSPs) in non-alcoholic fatty liver disease (NAFLD): from molecular mechanisms to therapeutic avenues.Biomarker research · 2024Review
- Prognostic Impact of Metabolic Syndrome and Steatotic Liver Disease in Hepatocellular Carcinoma Using Machine Learning Techniques.Metabolites · 2024Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Harmful algal bloom toxin microcystin has been associated with metabolic dysfunction-associated steatotic liver disease (MASLD) progression and hepatocellular carcinoma, though the mechanisms remain unclear. Using an established mouse model of MASLD, we show that the NLRP3-Hsp70-TLR4 axis drives in part the inflammation of the liver lobule that results in the progression of MASLD to metabolic dysfunction-associated steatohepatitis (MASH). Results showed that mice deficient in NLRP3 exhibited decreased MASH pathology, blocked Hsp70 expression, and co-binding with NLRP3, a crucial protein component of the liver inflammasome. Hsp70, both in the liver lobule and extracellularly released in the liver vasculature, acted as a ligand to TLR4 in the liver, primarily in hepatocytes to activate the NF-κB pathway, ultimately leading to hepatic cell death and necroptosis, a crucial pathology of MASH progression. The above studies show a novel insight into an inflammasome-triggered Hsp70-mediated inflammation that may have broader implications in MASLD pathology. MASLD to MASH progression often requires multiple hits. One of the mediators of progressive MASLD is environmental toxins. In this research report, we show for the first time a novel mechanism where microcystin-LR, an environmental toxin, advances MASLD to MASH by triggering the release of Hsp70 as a DAMP to activate TLR4-induced inflammation in the liver.
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What OpenQuestion holds
Registered trials
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.