Targeting LOXL1-expressing Hepatic Stellate Cell Inhibits Fibrogenesis and Sinusoid Angiogenesis via LOXL1/RUNX1/VEGFA Axis During Progression of Liver Fibrosis
LOXL1 in HSCs modulated ECM composition changes in endothelial cells in coculture studies. LOXL1 loss in HSCs suppressed HSC activation, LSEC capillarization, and macrophage infiltration, improved ECM remodeling, and attenuated liver fibrosis in HFCDAA-fed and CCl<sub>4</sub>-exposed mice. Our RNA sequencing data, corroborated by public database analyses, indicated RUNX family transcription factor 1 (RUNX1) was implicated in HSC activation and LOXL1-mediated angiogenesis. We propose that LOXL1 enhances HSC activation and LSEC capillarization through the RUNX 1/vascular endothelial growth factor A signaling axis CONCLUSIONS: Our study reveals novel mechanistic insights into liver fibrosis, highlighting HSC-derived LOXL1 as a central modulator of disease initiation and progression. Targeting the LOXL1/RUNX1/vascular endothelial growth factor A axis offers a promising therapeutic strategy for liver fibrosis.
Authors
- Albert Yang
- Fan Xu (ORCID: https://orcid.org/0000-0003-2758-3114)
- Xuzhen Yan (ORCID: https://orcid.org/0009-0003-1418-3821)
- Hong You (ORCID: https://orcid.org/0000-0001-9409-1158)
- Yiwen Wang (ORCID: https://orcid.org/0000-0003-2069-6685)
- Qi Han (ORCID: https://orcid.org/0000-0002-2140-4536)
- Ning Zhang (ORCID: https://orcid.org/0000-0003-1207-2573)
- Wei Chen (ORCID: https://orcid.org/0000-0003-4017-9722)
- Weiyu Li (ORCID: https://orcid.org/0000-0002-5261-5715)
Institutions
- National Clinical Research Center for Digestive Diseases (CN)
Publication Details
- Journal
- Cellular and Molecular Gastroenterology and Hepatology
- Published
- 2025-09-25
- DOI
- https://doi.org/10.1016/j.jcmgh.2025.101637
- Citations
- 2
- Primary Topic
- Microbial metabolism and enzyme function
- Type
- article
- Field-Weighted Citation Impact
- 1.61