Affiliation:
1. Liver Research Center, Beijing Friendship Hospital Capital Medical University Beijing China
2. Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis National Clinical Research Center of Digestive Diseases Beijing China
3. Emory National primate Research Center Emory University Atlanta Georgia USA
4. Beijing Clinical Research Institute Beijing China
5. Experimental and Translational Research Center, Beijing Friendship Hospital Capital Medical University Beijing China
Abstract
ObjectivesAortic 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.MethodsDysregulation 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).ResultsAEBP1 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.ConclusionA 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.
Funder
National Natural Science Foundation of China
National Science and Technology Major Project