ArticleBiomolecules2019
Inhibiting Extracellular Cathepsin D Reduces Hepatic Steatosis in Sprague⁻Dawley Rats
Article in Biomolecules, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Cathepsin D-driven IL2RG-JAK2 signal hijacking disrupts hepatic insulin action: mechanism-grounded proof that targeting cathepsin D prevents prediabetes.International journal of obesity (2005) · 2026Article
- Acute pancreatitis: mechanisms and therapeutic approaches.Signal transduction and targeted therapy · 2026Review
- Inhibition of intracellular versus extracellular cathepsin D differentially alters the liver lipidome of mice with metabolic dysfunction-associated steatohepatitis.The FEBS journal · 2025Article
- Intra and inter-organ communication through extracellular vesicles in obesity: functional role of obesesomes and steatosomes.Journal of translational medicine · 2025Article
- Asparagine-related biomarkers and regulatory mechanisms in type 2 diabetes mellitus.Frontiers in molecular biosciences · 2025Article
- Myosteatosis: Diagnosis, pathophysiology and consequences in metabolic dysfunction-associated steatotic liver disease.JHEP reports : innovation in hepatology · 2024Review
- Diagnostic indicators and lifestyle interventions of metabolic-associated fatty liver disease.Frontiers in nutrition · 2024Review
- Overview of multifunctional cysteinyl cathepsins in atherosclerosis-based cardiovascular disease: from insights into molecular functions to clinical implications.Cell & bioscience · 2023Review
- All Roads Lead to Cathepsins: The Role of Cathepsins in Non-Alcoholic Steatohepatitis-Induced Hepatocellular Carcinoma.Biomedicines · 2022Review
- Impact of Sarcopenia and Myosteatosis in Non-Cirrhotic Stages of Liver Diseases: Similarities and Differences across Aetiologies and Possible Therapeutic Strategies.Biomedicines · 2022Review
- Inhibition of Extracellular Cathepsin D Reduces Hepatic Lipid Accumulation and Leads to Mild Changes in Inflammationin NASH Mice.Frontiers in immunology · 2021Article
- Review
- Cathepsins in the Pathophysiology of Mucopolysaccharidoses: New Perspectives for Therapy.Cells · 2020Review
- NAFLD Preclinical Models: More than a Handful, Less of a Concern?Biomedicines · 2020Review
- Plasma cathepsin D activity is negatively associated with hepatic insulin sensitivity in overweight and obese humans.Diabetologia · 2020Article
- Plasma Cathepsin D Activity Rather Than Levels Correlates With Metabolic Parameters of Type 2 Diabetes in Male Individuals.Frontiers in endocrinology · 2020Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dietary and lifestyle changes are leading to an increased occurrence of non-alcoholic fatty liver disease (NAFLD). Using a hyperlipidemic murine model for non-alcoholic steatohepatitis (NASH), we have previously demonstrated that the lysosomal protease cathepsin D (CTSD) is involved with lipid dysregulation and inflammation. However, despite identifying CTSD as a major player in NAFLD pathogenesis, the specific role of extracellular CTSD in NAFLD has not yet been investigated. Given that inhibition of intracellular CTSD is highly unfavorable due to its fundamental physiological function, we here investigated the impact of a highly specific and potent small-molecule inhibitor of extracellular CTSD (CTD-002) in the context of NAFLD. Treatment of bone marrow-derived macrophages with CTD-002, and incubation of hepatic HepG2 cells with a conditioned medium derived from CTD-002-treated macrophages, resulted in reduced levels of inflammation and improved cholesterol metabolism. Treatment with CTD-002 improved hepatic steatosis in high fat diet-fed rats. Additionally, plasma levels of insulin and hepatic transaminases were significantly reduced upon CTD-002 administration. Collectively, our findings demonstrate for the first time that modulation of extracellular CTSD can serve as a novel therapeutic modality for NAFLD.
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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.