肝星状细胞
纤维化
癌症研究
基因沉默
基因敲除
小RNA
胆管上皮细胞
生物
医学
内科学
基因
遗传学
作者
Wen Zhang,Yujia Li,Ning Zhang,Shuyan Chen,Xiaofei Tong,Bingqiong Wang,Tao Huang,Hong You,Wei Chen
标识
DOI:10.1111/1751-2980.13230
摘要
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 was specifically associated with liver fibrosis and was related to a poor prognosis and predicted the role of AEBP1 in HSCs, providing a new insight for understanding AEBP1 in liver fibrosis.
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