ArticleJCI insight2024
Liver sinusoidal endothelial cells contribute to portal hypertension through collagen type IV-driven sinusoidal remodeling.
Article in JCI insight, 2024. 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.
- Epigenetically controlled endothelial promyelocytic leukemia drives liver inflammation and fibrosis.The Journal of clinical investigation · 2026Article
- [SingleZhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026Article
- [Dual-wavelength photoacoustic microscopy for evaluation of microcirculatory dysfunction and spatial heterogeneity in mice with liver fibrosis].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- [Research progress on cellular senescence and liver diseases].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026Review
- Toxic lipid-induced epigenetic activation of ICAM1 in liver sinusoidal endothelium regulates myeloid-driven fibro-inflammatory response in MASH.Hepatology (Baltimore, Md.) · 2026Article
- Experimental pulmonary arterial hypertension in mice with a pathogenic SOX17 variant.Scientific reports · 2026Article
- Loss of β-catenin in cholangiocytes promotes hepatocyte reprogramming and vascular remodeling during murine cholestasis.Cell communication and signaling : CCS · 2026Article
- Review
- Multimodal assessment of liver stiffness and portal hemodynamics in a cirrhotic mouse model.Frontiers in bioengineering and biotechnology · 2026Article
- Epigenetic reprogramming of hepatic antigen presenting cells in chronic liver disease.Frontiers in immunology · 2026Review
- Inflammation and immunity in liver homeostasis and disease: a nexus of hepatocytes, nonparenchymal cells and immune cells.Cellular & molecular immunology · 2025Review
- Deciphering Age-Dependent ECM Remodelling in Liver: Proteomic Profiling and Its Implications for Aging and Therapeutic Targets.Cell proliferation · 2025Article
- APJ regulates the balance between self-renewal and differentiation of vascular endothelial stem cells.Inflammation and regeneration · 2025Article
- Hepatic stellate cells: balancing homeostasis, hepatoprotection and fibrogenesis in health and disease.Nature reviews. Gastroenterology & hepatology · 2025Review
- Non-parenchymal cells: key targets for modulating chronic liver diseases.Frontiers in immunology · 2025Review
- Spleen stiffness measurements during recompensation in patients with acutely decompensated liver cirrhosis: preliminary findings of a pilot study.Frontiers in medicine · 2024Article
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Authors and funding
13 authors.
Funding
Abstract
Portal hypertension (PHTN) is a severe complication of liver cirrhosis and is associated with intrahepatic sinusoidal remodeling induced by sinusoidal resistance and angiogenesis. Collagen type IV (COL4), a major component of basement membrane, forms in liver sinusoids upon chronic liver injury. However, the role, cellular source, and expression regulation of COL4 in liver diseases are unknown. Here, we examined how COL4 is produced and how it regulates sinusoidal remodeling in fibrosis and PHTN. Human cirrhotic liver sample RNA sequencing showed increased COL4 expression, which was further verified via immunofluorescence staining. Single-cell RNA sequencing identified liver sinusoidal endothelial cells (LSECs) as the predominant source of COL4 upregulation in mouse fibrotic liver. In addition, COL4 was upregulated in a TNF-α/NF-κB-dependent manner through an epigenetic mechanism in LSECs in vitro. Indeed, by utilizing a CRISPRi-dCas9-KRAB epigenome-editing approach, epigenetic repression of the enhancer-promoter interaction showed silencing of COL4 gene expression. LSEC-specific COL4 gene mutation or repression in vivo abrogated sinusoidal resistance and angiogenesis, which thereby alleviated sinusoidal remodeling and PHTN. Our findings reveal that LSECs promote sinusoidal remodeling and PHTN during liver fibrosis through COL4 deposition.
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