Mapping vascular plasticity during fibrogenesis identifies fibrosis-associated endothelial cells in early-stage liver disease
5 affiliations
- 1William Harvey Research Institute and
- 2Blizard Institute, Queen Mary University London, London, United Kingdom.
- 3University of Manchester, Manchester, United Kingdom.
- 4Manchester University NHS Foundation Trust, Manchester, England, United Kingdom.
- 5Centre for Inflammation Research, Institute for Regeneration & Repair, University of Edinburgh, Edinburgh, United Kingdom.
Abstract
Vascular plasticity is a crucial biological asset enabling our bodies to rapidly adapt to infections and acute inflammation. However, repeated insults during chronic disease can result in these vascular adaptations becoming irreversible, thereby driving disease progression and fibrosis. This study aimed to understand if phenotypic changes in endothelial cell (EC) identity could be indicative of progressive fibrosis and thereby offer diagnostic and therapeutic opportunities for patients with metabolic dysfunction–associated steatotic liver disease (MASLD). We integrated high-resolution imaging and proteomic and transcriptomic analysis, which collectively highlighted a central role for endothelial-mesenchymal transition–induced (EndMT-induced) EC plasticity in the derivation of fibrosis-associated EC (FAEC). We demonstrated that: (a) full-spectrum flow cytometry can provide new opportunities to categorize and phenotype EC subpopulations; (b) 2 distinct EndMT-derived FAEC subpopulations expanded during fibrogenesis (THY1.2+ICAM1+ and TAGLN+MCAM+ EC) that displayed unique immunomodulatory and metabolic phenotypes; (c) TAGLN+ FAEC are a conserved, profibrotic cell type that arose at early stages of MASLD; and (d) increased hepatic expression of TAGLN was significantly associated with detrimental patient outcomes at all stages of liver disease. This study paves the way for the development of FAEC-specific diagnostic and therapeutic approaches to tackle progressive fibrotic disease.
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BibTeX
@article{gkantsinikoudi2026mapping,
title = {{Mapping vascular plasticity during fibrogenesis identifies fibrosis-associated endothelial cells in early-stage liver disease}},
author = {Christina Gkantsinikoudi and Joshua P. Dignam and Raju Kumar and Elliot Jokl and Meenakshi Rana and Wenhao Li and Maryna Samus and Stephanie Landi and Varinder S. Athwal and Timothy J. Kendall and Antal Rot and Jonathan A. Fallowfield and Karen Piper Hanley and William Alazawi and Neil P. Dufton},
journal = {JCI Insight},
year = {2026},
month = sep,
doi = {10.1172/jci.insight.207327},
url = {https://doi.org/10.1172/jci.insight.207327},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Mapping vascular plasticity during fibrogenesis identifies fibrosis-associated endothelial cells in early-stage liver disease
AU - Christina Gkantsinikoudi
AU - Joshua P. Dignam
AU - Raju Kumar
AU - Elliot Jokl
AU - Meenakshi Rana
AU - Wenhao Li
AU - Maryna Samus
AU - Stephanie Landi
AU - Varinder S. Athwal
AU - Timothy J. Kendall
AU - Antal Rot
AU - Jonathan A. Fallowfield
AU - Karen Piper Hanley
AU - William Alazawi
AU - Neil P. Dufton
PY - 2026
DA - 2026/09/01
JO - JCI Insight
DO - 10.1172/jci.insight.207327
UR - https://doi.org/10.1172/jci.insight.207327
AB - Vascular plasticity is a crucial biological asset enabling our bodies to rapidly adapt to infections and acute inflammation. However, repeated insults during chronic disease can result in these vascular adaptations becoming irreversible, thereby driving disease progression and fibrosis. This study aimed to understand if phenotypic changes in endothelial cell (EC) identity could be indicative of progressive fibrosis and thereby offer diagnostic and therapeutic opportunities for patients with metabolic dysfunction–associated steatotic liver disease (MASLD). We integrated high-resolution imaging and proteomic and transcriptomic analysis, which collectively highlighted a central role for endothelial-mesenchymal transition–induced (EndMT-induced) EC plasticity in the derivation of fibrosis-associated EC (FAEC). We demonstrated that: (a) full-spectrum flow cytometry can provide new opportunities to categorize and phenotype EC subpopulations; (b) 2 distinct EndMT-derived FAEC subpopulations expanded during fibrogenesis (THY1.2+ICAM1+ and TAGLN+MCAM+ EC) that displayed unique immunomodulatory and metabolic phenotypes; (c) TAGLN+ FAEC are a conserved, profibrotic cell type that arose at early stages of MASLD; and (d) increased hepatic expression of TAGLN was significantly associated with detrimental patient outcomes at all stages of liver disease. This study paves the way for the development of FAEC-specific diagnostic and therapeutic approaches to tackle progressive fibrotic disease.
SN - 2379-3708
ER -