Targeting LOXL1-expressing Hepatic Stellate Cell Inhibits Fibrogenesis and Sinusoid Angiogenesis via LOXL1/RUNX1/VEGFA Axis During Progression of Liver Fibrosis

作者：Xuzhen Yan, Qi Han, Yiwen Wang, Weiyu Li, Ning Zhang, Fan Xu, Wei Chen, Hong You, Aiting Yang · 发表于：Cellular and Molecular Gastroenterology and Hepatology · 年份：2025 · DOI：10.1016/j.jcmgh.2025.101637 · 被引用次数：4 · 研究领域：Microbial metabolism and enzyme function、Liver physiology and pathology、Alcohol Consumption and Health Effects

BACKGROUND & AIMS: Hepatic stellate cells (HSCs) are the major source of excessive production of extracellular matrix (ECM) proteins and act as a hub for intrahepatic fibrosis signaling. Although extensive crosstalk between HSCs and liver sinusoidal endothelial cells (LSECs) significantly influences disease progression, the detailed mechanisms remain poorly understood. Here, we investigated the role of lysyl oxidase-like 1 (LOXL1), a pivotal enzyme in ECM cross-linking, in crosstalk between HSCs and LSECs during liver fibrosis. METHODS: ) exposure. Liver samples were assessed by histology, scanning electron microscopy, immunostaining, and quantitative polymerase chain reaction (qPCR). Liver tissue and HSCs were analyzed by RNA sequencing to study LOXL1's mechanisms regulating liver fibrosis. RESULTS: -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.