Fibroblast‐specific adipocyte enhancer binding protein 1 is a potential pathological trigger and prognostic marker for liver fibrosis independent of etiology

作者：Wen Zhang, Yu Jia Li, Ning Zhang, Shu Yan Chen, Xiao Fei Tong, Bing Qiong Wang, Tao Huang, Hong You, Wei Chen · 发表于：Journal of Digestive Diseases · 年份：2023 · DOI：10.1111/1751-2980.13230 · 被引用次数：14 · 研究领域：Liver physiology and pathology、Liver Disease Diagnosis and Treatment、NF-κB Signaling Pathways

OBJECTIVES: Aortic carboxypeptidase-like protein (ACLP) is an extracellular protein involved in adipogenesis, epithelial-mesenchymal transition, epithelial cell hyperplasia, and collagen fibrogenesis. This study mainly aimed to analyze the potential role of adipocyte enhancer binding protein 1 (AEBP1), the ACLP-encoding gene, as a pathological target or prognostic marker for liver fibrosis regardless of etiology. METHODS: Dysregulation pattern, clinical relevance, and biological significance of AEBP1 gene in liver fibrosis were analyzed using publicly available transcriptomic profiles, different liver fibrosis mouse models, biological databases, and AEBP1 gene silencing followed by RNA sequencing in human hepatic stellate cells (HSCs). RESULTS: AEBP1 gene expression was upregulated and positively correlated with liver fibrogenesis independent of etiology, the protein of which was further verified in liver fibrosis mouse models induced by different pathogenic factors. A higher expression of liver AEBP1 gene had the potential to predict poor prognosis in liver fibrosis. Systematic bioinformatic analyses revealed that AEBP1 expression was HSCs-specific and associated with extracellular matrix (ECM) remodeling and its downstream mechanical-chemical signaling transition. AEBP1 knockdown by specific small interfering RNAs (siRNAs) in HSCs inhibited ECM-receptor interaction and immune-related pathways as well as HSC proliferation or activation. CONCLUSION: A high expression of AEBP1...