ArticleNature biomedical engineering2023
Advanced glycation end-products as mediators of the aberrant crosslinking of extracellular matrix in scarred liver tissue.
Article in Nature biomedical engineering, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
What it found
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Who cites it
42 citing papers in PubMed, 55 citations in OpenAlex.
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- Defective efferocytosis in diabetes: molecular mechanisms and emerging therapeutic strategies.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- High-Fat-Diet-Induced Hyperglycemia Alters Liver Extracellular Matrix Composition in Mice Model.Cells · 2026Article
- Histaminylation alters collagen matrix mechanics and attenuates cardiac fibrosis post-myocardial infarction via mechanotransduction signaling axis.Signal transduction and targeted therapy · 2026Article
- Metabolic dysfunction-associated steatotic liver disease and steatohepatitis-associated hepatocarcinoma preclinical models.Nature reviews. Gastroenterology & hepatology · 2026Review
- Mechanobiological research fueling the advancement of mechanotherapy and mechanohealth.Mechanobiology in medicine · 2026Article
- Chemomechanical remodeling of glucocorticoid-sensitive fibroblasts for multimodal synergistic therapy of skin fibrosis.Cell reports. Medicine · 2026Article
- Stimuli-responsive hydrogels based on cascade reactions: a novel strategy to promote the efficient repair of diabetic wounds.Theranostics · 2026Review
- Nanomedicine-Driven Modulation of Signaling Pathways in Hepatic Fibrosis.International journal of nanomedicine · 2026Review
- Nanozymes for extracellular matrix and cell sheet engineering: biomedical potential and complementary enzymatic strategies.Frontiers in molecular biosciences · 2026Review
- He-He-Shu-Yang formula alleviates liver fibrosis by inhibiting hepatic stellate cell activationWorld journal of hepatology · 2025Article
- Causal pathways of plasma metabolites: unveiling metabolic associations in liver diseases.Nutrition & metabolism · 2025Article
- Advanced cell-adaptable hydrogels for bioprinting.Bioactive materials · 2025Review
- Constructing biomimetic microenvironments for liver regeneration.Journal of nanobiotechnology · 2025Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
The extracellular matrix of cirrhotic liver tissue is highly crosslinked. Here we show that advanced glycation end-products (AGEs) mediate crosslinking in liver extracellular matrix and that high levels of crosslinking are a hallmark of cirrhosis. We used liquid chromatography-tandem mass spectrometry to quantify the degree of crosslinking of the matrix of decellularized cirrhotic liver samples from patients and from two mouse models of liver fibrosis and show that the structure, biomechanics and degree of AGE-mediated crosslinking of the matrices can be recapitulated in collagen matrix crosslinked by AGEs in vitro. Analyses via cryo-electron microscopy and optical tweezers revealed that crosslinked collagen fibrils form thick bundles with reduced stress relaxation rates; moreover, they resist remodelling by macrophages, leading to reductions in their levels of adhesion-associated proteins, altering HDAC3 expression and the organization of their cytoskeleton, and promoting a type II immune response of macrophages. We also show that rosmarinic acid inhibited AGE-mediated crosslinking and alleviated the progression of fibrosis in mice. Our findings support the development of therapeutics targeting crosslinked extracellular matrix in scarred liver tissue.
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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.