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

Abstract

Aimthe aortic carboxypeptidase‐like protein (ACLP) is an extracellular protein involved in adipogenesis, epithelial‐mesenchymal transition, epithelial cell hyperplasia and collagen fibrogenesis. The main study objective was to analyze the potential of ACLP encoding gene (AEBP1) 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 silence followed by RNA sequencing in human hepatic stellate cells (HSCs).ResultsAEBP1 gene was upregulated and positively correlated with liver fibrogenesis independent of any etiology, the protein of which was further verified in liver fibrosis mouse models induced by different pathogenic factors. Higher expression of liver AEBP1 gene had potential to predict poor prognosis in liver fibrosis. Systematical bioinformatics analyses revealed AEBP1 expression was HSCs‐specific and associated with ECM remodeling and its downstream mechanical‐chemical signaling transition. AEBP1 knockdown by specific siRNAs in HSCs inhibited ECM‐receptor interaction and immune‐related pathways as well as HSCs proliferation or activation.Conclusionsour current study confirmed high expression of AEBP1 was specifically associated with liver fibrosis and predicted its poor prognosis and the role of AEBP1 in HSCs, providing a new insight for understanding AEBP1 in liver fibrosis.This article is protected by copyright. All rights reserved.

G-quadruplex forming regions inGCKandTM6SF2are targets for differential DNA methylation in metabolic disease and hepatocellular carcinoma patients

“…GCK is located in a topological associated domain (TAD) of approximately 500 kb. Strikingly, within this TAD several genes are known for their association with metabolic diseases and cancer like AE binding protein 1 (AEBP1) 85,86 , YKT6 v-SNARE homolog (YKT6) 87,88 , upregulator of cell proliferation (URGCP) 89,90 and phosphoglycerate mutase 2 (PGAM2; for more details see Supplement Section 4) 91 .…”