Fucosyltransferase 8 is associated with post-thrombotic vein wall fibrosis and macrophage profibrotic signaling.
- 1Department of Vascular Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
- 2The Affiliated Chuzhou Hospital of Anhui Medical University, The Fifth Clinical Medical College of Anhui Medical University, Chuzhou, Anhui, China.
Abstract
Objective
To investigate the role of fucosyltransferase 8 (FUT8) in post-thrombotic (PT) vein wall fibrosis and to clarify its association with focal adhesion kinase (FAK)/extracellular signal-regulated kinase (ERK) signaling in macrophage-mediated fibrotic remodeling.Methods
A murine model of venous thrombosis was established by partial ligation of the inferior vena cava, followed by in vivo intervention with the FUT8 inhibitor 2F-peracetyl-fucose. Histological staining, immunohistochemistry, lectin-based fluorescence staining, and immunofluorescence were used to assess vein wall remodeling, collagen deposition, core fucosylation, and macrophage localization. In vitro, a FUT8-overexpressing (OE) RAW264.7 (murine macrophage cell line) macrophage cell line was used to evaluate cell metabolic viability, adhesion to fibronectin, migration, FAK/ERK signaling, and profibrotic molecule expression. Conditioned medium from macrophages was applied to NIH3T3 (mouse embryonic fibroblast cell line) fibroblasts to evaluate paracrine effects on migration and extracellular matrix expression. To assess the involvement of macrophage ERK signaling, Vector and FUT8-OE macrophages were pretreated with the ERK inhibitor SCH772984 or vehicle, washed, and cultured in inhibitor-free medium before conditioned-medium collection.Results
FUT8 expression and core fucosylation levels were increased in PT vein wall tissues, with FUT8 signal observed in infiltrating macrophages. 2F-peracetyl-fucose treatment reduced vein wall thickening and collagen accumulation in vivo. In RAW264.7 macrophages, FUT8-OE was associated with enhanced adhesion to fibronectin, impaired migration, increased FAK and ERK phosphorylation, and increased fibronectin 1 (FN1) expression. Conditioned medium from FUT8-OE macrophages promoted fibroblast migration and increased collagen type 1 and FN1 expression. SCH772984 pretreatment of FUT8-OE macrophages attenuated the subsequent conditioned-medium-induced increases in fibroblast collagen type 1 and FN1 protein and mRNA expression.Conclusions
FUT8 is associated with macrophage phenotypic remodeling and profibrotic conditioned-medium effects after venous thrombosis. The attenuation of fibroblast matrix responses after ERK inhibition in FUT8-OE macrophages supports the involvement of macrophage ERK signaling in this phenotype. These findings support FUT8 as a candidate molecular target for further mechanistic investigation in PT vein wall fibrosis.Clinical relevance
Post-thrombotic (PT) syndrome is a long-term complication of deep vein thrombosis characterized in part by persistent vein wall fibrosis. Current therapies mainly address venous obstruction and reflux rather than structural vein wall remodeling. Fucosyltransferase 8 (FUT8) expression was increased in PT vein walls and localized to infiltrating macrophages. In mice, 2F-peracetyl-fucose treatment attenuated vein wall thickening and collagen deposition, whereas extracellular signal-regulated kinase inhibition in FUT8-overexpressing macrophages reduced conditioned-medium-induced fibroblast matrix responses. These findings support FUT8-associated signaling as a candidate pathway for further investigation in PT fibrosis.
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BibTeX
@article{du2026fucosyltransferase,
title = {{Fucosyltransferase 8 is associated with post-thrombotic vein wall fibrosis and macrophage profibrotic signaling.}},
author = {Guodong Du and Yu Jin and Hongji Pu and Xin Wang and Xinrui Yang and Xinwu Lu and Ruihua Wang},
journal = {JVS-vascular science},
year = {2026},
month = sep,
doi = {10.1016/j.jvssci.2026.100446},
url = {https://europepmc.org/article/MED/42959544},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Fucosyltransferase 8 is associated with post-thrombotic vein wall fibrosis and macrophage profibrotic signaling.
AU - Guodong Du
AU - Yu Jin
AU - Hongji Pu
AU - Xin Wang
AU - Xinrui Yang
AU - Xinwu Lu
AU - Ruihua Wang
PY - 2026
DA - 2026/09/16
JO - JVS-vascular science
DO - 10.1016/j.jvssci.2026.100446
UR - https://europepmc.org/article/MED/42959544
AB - Objective To investigate the role of fucosyltransferase 8 (FUT8) in post-thrombotic (PT) vein wall fibrosis and to clarify its association with focal adhesion kinase (FAK)/extracellular signal-regulated kinase (ERK) signaling in macrophage-mediated fibrotic remodeling.Methods A murine model of venous thrombosis was established by partial ligation of the inferior vena cava, followed by in vivo intervention with the FUT8 inhibitor 2F-peracetyl-fucose. Histological staining, immunohistochemistry, lectin-based fluorescence staining, and immunofluorescence were used to assess vein wall remodeling, collagen deposition, core fucosylation, and macrophage localization. In vitro, a FUT8-overexpressing (OE) RAW264.7 (murine macrophage cell line) macrophage cell line was used to evaluate cell metabolic viability, adhesion to fibronectin, migration, FAK/ERK signaling, and profibrotic molecule expression. Conditioned medium from macrophages was applied to NIH3T3 (mouse embryonic fibroblast cell line) fibroblasts to evaluate paracrine effects on migration and extracellular matrix expression. To assess the involvement of macrophage ERK signaling, Vector and FUT8-OE macrophages were pretreated with the ERK inhibitor SCH772984 or vehicle, washed, and cultured in inhibitor-free medium before conditioned-medium collection.Results FUT8 expression and core fucosylation levels were increased in PT vein wall tissues, with FUT8 signal observed in infiltrating macrophages. 2F-peracetyl-fucose treatment reduced vein wall thickening and collagen accumulation in vivo. In RAW264.7 macrophages, FUT8-OE was associated with enhanced adhesion to fibronectin, impaired migration, increased FAK and ERK phosphorylation, and increased fibronectin 1 (FN1) expression. Conditioned medium from FUT8-OE macrophages promoted fibroblast migration and increased collagen type 1 and FN1 expression. SCH772984 pretreatment of FUT8-OE macrophages attenuated the subsequent conditioned-medium-induced increases in fibroblast collagen type 1 and FN1 protein and mRNA expression.Conclusions FUT8 is associated with macrophage phenotypic remodeling and profibrotic conditioned-medium effects after venous thrombosis. The attenuation of fibroblast matrix responses after ERK inhibition in FUT8-OE macrophages supports the involvement of macrophage ERK signaling in this phenotype. These findings support FUT8 as a candidate molecular target for further mechanistic investigation in PT vein wall fibrosis.Clinical relevance Post-thrombotic (PT) syndrome is a long-term complication of deep vein thrombosis characterized in part by persistent vein wall fibrosis. Current therapies mainly address venous obstruction and reflux rather than structural vein wall remodeling. Fucosyltransferase 8 (FUT8) expression was increased in PT vein walls and localized to infiltrating macrophages. In mice, 2F-peracetyl-fucose treatment attenuated vein wall thickening and collagen deposition, whereas extracellular signal-regulated kinase inhibition in FUT8-overexpressing macrophages reduced conditioned-medium-induced fibroblast matrix responses. These findings support FUT8-associated signaling as a candidate pathway for further investigation in PT fibrosis.
SN - 2666-3503
ER -