ArticleMolecular metabolism2024
Cathepsin D is essential for the degradomic shift of macrophages required to resolve liver fibrosis.
Article in Molecular metabolism, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- An Immunocompetent Hepatic Organoid Model Reveals Conserved Hepatic Immune Dysregulation DuringInternational journal of molecular sciences · 2026Article
- Reprogramming macrophages to treat liver diseases.Hepatology (Baltimore, Md.) · 2026Review
- Anticancer Activity of the Antimicrobial Myristoylated Peptide Myr-B in HeLa Cells: Cytotoxic, Membrane-Disruptive and Proteomic Insights.International journal of molecular sciences · 2026Article
- Metabolomics Highlights Reduced Glutamate and Acetylcarnitine in the Amniotic Fluid of Cytomegalovirus-Infected Pregnant Women.Journal of proteome research · 2026Article
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- Dual molecular and clinical machine-learning prognostic modeling in pancreatic ductal adenocarcinoma: a chaperone-mediated autophagy-based framework integrating multi-cohort molecular signatures and a single-center clinical nomogram.Frontiers in cell and developmental biology · 2026Article
- Article
- Heterogeneity of Extracellular Vesicles and Non-Vesicular Nanoparticles in Glioblastoma.Journal of extracellular vesicles · 2025Article
- Transglutaminase 2-expressing macrophages modulate adipose tissue inflammation.Communications biology · 2025Article
- Neuroglobin regulates autophagy through mTORC1/RAPTOR/ULK-1 pathway in human neuroblastoma cells.Scientific reports · 2025Article
- Molecular Insights into the Interaction of Cathepsin D and Iron in Chronic Wound Healing: Exploring Therapeutic Potential and Mechanisms.Biomedicines · 2025Article
- The role of α-hydroxybutyrate in modulating sepsis progression: identification of key targets and biomarkers through multi-database data mining, machine learning, and unsupervised clustering.Frontiers in pharmacology · 2025Article
- Bidirectional crosstalk between the bone extracellular matrix and lysosomes in bone remodeling and osteoporosis.Frontiers in endocrinology · 2025Review
- Editorial: Immunomics of the immune regulatory networks in the one health perspective.Frontiers in immunology · 2024Article
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Authors and funding
21 authors.
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No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectivesFibrosis contributes to 45% of deaths in industrialized nations and is characterized by an abnormal accumulation of extracellular matrix (ECM). There are no specific anti-fibrotic treatments for liver fibrosis, and previous unsuccessful attempts at drug development have focused on preventing ECM deposition. Because liver fibrosis is largely acknowledged to be reversible, regulating fibrosis resolution could offer novel therapeutical options. However, little is known about the mechanisms controlling ECM remodeling during resolution. Changes in proteolytic activity are essential for ECM homeostasis and macrophages are an important source of proteases. Herein, in this study we evaluate the role of macrophage-derived cathepsin D (CtsD) during liver fibrosis.
methodsCtsD expression and associated pathways were characterized in single-cell RNA sequencing and transcriptomic datasets in human cirrhosis. Liver fibrosis progression, reversion and functional characterization were assessed in novel myeloid-CtsD and hepatocyte-CtsD knock-out mice.
resultsAnalysis of single-cell RNA sequencing datasets demonstrated CtsD was expressed in macrophages and hepatocytes in human cirrhosis. Liver fibrosis progression, reversion and functional characterization were assessed in novel myeloid-CtsD (CtsD
conclusionsOur work describes for the first-time CtsD-driven lysosomal activity as a central hub for restorative macrophage function during fibrosis resolution and opens new avenues to explore their degradome landscape to inform drug development.
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