ArticleCardiovascular research2022
Endothelial Zeb2 preserves the hepatic angioarchitecture and protects against liver fibrosis.
Article in Cardiovascular research, 2022. 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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Who cites it
32 citing papers in PubMed, 53 citations in OpenAlex.
- Role of ZEB1 in angiogenesis and therapeutic potential (Review).International journal of molecular medicine · 2026Review
- Xuefu Zhuyu Decoction Reduces Excessive Collagen Deposition and Crosslinking in Myocardial Fibrosis via CTR1-Copper-LOX Axis.Chinese journal of integrative medicine · 2026Article
- Sinusoidal endothelial cells control liver inflammation and fibrosis.The Journal of clinical investigation · 2026Article
- Spermidine suppresses liver fibrosis by remodeling the communication signal between liver sinusoidal endothelial cells and hepatic stellate cells.Cell death discovery · 2026Article
- Proteomics reveals the key transcription-related factors mediating obstructive nephropathy in pediatric patients and mice.Renal failure · 2025Article
- Global research trends in liver regeneration and immunomodulation: A perspective from bibliometric analysis.Human vaccines & immunotherapeutics · 2025Article
- Single-Cell Transcriptomic Analysis of Different Liver Fibrosis Models: Elucidating Molecular Distinctions and Commonalities.Biomedicines · 2025Article
- Loss of endothelial ZEB2 in mice attenuates steatosis early during metabolic dysfunction-associated steatotic liver disease.Scientific reports · 2025Article
- Review
- Autocrine GDF10 Inhibits Hepatic Stellate Cell Activation via BMPR2/ALK3 Receptor to Prevent Liver Fibrosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Orientin: a comprehensive review of a promising bioactive flavonoid.Inflammopharmacology · 2025Review
- Dualistic role of ZEB1 and ZEB2 in tumor progression.Biology direct · 2025Review
- The role of liver sinusoidal endothelial cells in metabolic dysfunction-associated steatotic liver diseases and liver cancer: mechanisms and potential therapies.Angiogenesis · 2025Review
- Dynamic crosstalk between HSCs and liver microenvironment: multicellular interactions in the regulation of liver fibrosis.Frontiers in cell and developmental biology · 2025Review
- Si-Wu-Tang improves liver fibrosis by restoring liver sinusoidal endothelial cell functionality and reducing communication with hepatic stellate cells.Chinese medicine · 2024Article
- Angiocrine signaling in sinusoidal homeostasis and liver diseases.Journal of hepatology · 2024Review
- Liver sinusoidal endothelial cell: An important yet often overlooked player in the liver fibrosis.Clinical and molecular hepatology · 2024Review
- Role of liver sinusoidal endothelial cell in metabolic dysfunction-associated fatty liver disease.Cell communication and signaling : CCS · 2024Review
- Liver specification of human iPSC-derived endothelial cells transplanted into mouse liver.JHEP reports : innovation in hepatology · 2024Article
- Integrative analysis of chromatin accessibility and transcriptome landscapes in the induction of peritoneal fibrosis by high glucose.Journal of translational medicine · 2024Article
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Authors and funding
27 authors at 10 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsHepatic capillaries are lined with specialized liver sinusoidal endothelial cells (LSECs) which support macromolecule passage to hepatocytes and prevent fibrosis by keeping hepatic stellate cells (HSCs) quiescent. LSEC specialization is co-determined by transcription factors. The zinc-finger E-box-binding homeobox (Zeb)2 transcription factor is enriched in LSECs. Here, we aimed to elucidate the endothelium-specific role of Zeb2 during maintenance of the liver and in liver fibrosis. METHODS AND
resultsTo study the role of Zeb2 in liver endothelium we generated EC-specific Zeb2 knock-out (ECKO) mice. Sequencing of liver EC RNA revealed that deficiency of Zeb2 results in prominent expression changes in angiogenesis-related genes. Accordingly, the vascular area was expanded and the presence of pillars inside ECKO liver vessels indicated that this was likely due to increased intussusceptive angiogenesis. LSEC marker expression was not profoundly affected and fenestrations were preserved upon Zeb2 deficiency. However, an increase in continuous EC markers suggested that Zeb2-deficient LSECs are more prone to dedifferentiation, a process called 'capillarization'. Changes in the endothelial expression of ligands that may be involved in HSC quiescence together with significant changes in the expression profile of HSCs showed that Zeb2 regulates LSEC-HSC communication and HSC activation. Accordingly, upon exposure to the hepatotoxin carbon tetrachloride (CCl4), livers of ECKO mice showed increased capillarization, HSC activation, and fibrosis compared to livers from wild-type littermates. The vascular maintenance and anti-fibrotic role of endothelial Zeb2 was confirmed in mice with EC-specific overexpression of Zeb2, as the latter resulted in reduced vascularity and attenuated CCl4-induced liver fibrosis.
conclusionEndothelial Zeb2 preserves liver angioarchitecture and protects against liver fibrosis. Zeb2 and Zeb2-dependent genes in liver ECs may be exploited to design novel therapeutic strategies to attenuate hepatic fibrosis.
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