Work

Mapping vascular plasticity during fibrogenesis identifies fibrosis-associated endothelial cells in early-stage liver disease

Year: 2026

Type: article

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.

Source: JCI Insight

DOI: 10.1172/jci.insight.207327