ArticleNature aging2023
Age-related liver endothelial zonation triggers steatohepatitis by inactivating pericentral endothelium-derived C-kit.
Article in Nature aging, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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32 citing papers in PubMed, 55 citations in OpenAlex.
- Proliferation dynamics of organotypic vascular endothelium during aging.NPJ cardiovascular health · 2026Article
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- Liver endothelial zonation orchestrates hepatic steatosis onset through retinoic acid-regulated FGF1.Science advances · 2026Article
- Kupffer cells: Orchestrators of liver physiology.Liver research (Beijing, China) · 2026Review
- Senescent cells in systemic aging: SASP heterogeneity, immune escape, and endocrine modulation.Biogerontology · 2026Review
- The cGAS-STING pathway in senescence and aging-related diseases: mechanisms and therapeutic opportunities.Cell communication and signaling : CCS · 2026Review
- Progressive fibrosis in human MASLD is associated with spatially linked transcriptomic signatures of metabolic reprogramming and senescence.JHEP reports : innovation in hepatology · 2026Article
- Spatial niche remodeling of senescent liver-resident immune cells and its role in chronic liver diseases.Frontiers in medicine · 2026Review
- Neutrophil extracellular traps-triggered hepatocellular senescence exacerbates lipotoxicity in non-alcoholic steatohepatitis.Journal of advanced research · 2026Article
- Key Experimental Therapeutics and Knowledge Gaps in Metabolic Dysfunction-Associated Steatohepatitis (MASH).Drug design, development and therapy · 2026Review
- Review
- Exploring the mechanism of plasticizers action in liver damage based on network toxicology, molecular docking, and molecular dynamic simulation.Scientific reports · 2025Article
- Molecular mechanisms in MASLD/MASH-related HCC.Hepatology (Baltimore, Md.) · 2025Review
- Tissue-Specific Effects of Dietary Protein on Cellular Senescence Are Mediated by Branched-Chain Amino Acids.Aging cell · 2025Article
- [Biological characteristics of liver zonation and its role in disease and aging].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2025Review
- Targeting the chromatin remodeler BAZ2B mitigates hepatic senescence and MASH fibrosis.Nature aging · 2025Article
- Aging and metabolic dysfunction-associated steatotic liver disease: a bidirectional relationship.Frontiers of medicine · 2025Review
- Quasi-spatial single-cell transcriptome based on physical tissue properties defines early aging associated niche in liver.Nature aging · 2025Article
- Molecular mechanisms in liver repair and regeneration: from physiology to therapeutics.Signal transduction and targeted therapy · 2025Review
- A perfusion-independent high-throughput method to isolate liver sinusoidal endothelial cells.Communications biology · 2025Article
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14 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Aging leads to systemic metabolic disorders, including steatosis. Here we show that liver sinusoidal endothelial cell (LSEC) senescence accelerates liver sinusoid capillarization and promotes steatosis by reprogramming liver endothelial zonation and inactivating pericentral endothelium-derived C-kit, which is a type III receptor tyrosine kinase. Specifically, inhibition of endothelial C-kit triggers cellular senescence, perturbing LSEC homeostasis in male mice. During diet-induced nonalcoholic steatohepatitis (NASH) development, Kit deletion worsens hepatic steatosis and exacerbates NASH-associated fibrosis and inflammation. Mechanistically, C-kit transcriptionally inhibits chemokine (C-X-C motif) receptor (CXCR)4 via CCAAT enhancer-binding protein α (CEBPA). Blocking CXCR4 signaling abolishes LSEC-macrophage-neutrophil cross-talk and leads to the recovery of C-kit-deficient mice with NASH. Of therapeutic relevance, infusing C-kit-expressing LSECs into aged mice or mice with diet-induced NASH counteracts age-associated senescence and steatosis and improves the symptoms of diet-induced NASH by restoring metabolic homeostasis of the pericentral liver endothelium. Our work provides an alternative approach that could be useful for treating aging- and diet-induced NASH.
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