Fibroblast-specific adipocyte enhancer binding protein 1 is a potential pathological trigger and prognostic marker for liver fibrosis independent of etiology
Fibroblast-specific adipocyte enhancer binding protein 1 is a potential pathological trigger and prognostic marker for liver fibrosis independent of etiology
复制标题
DOI：
10.1111/1751-2980.13230
复制
发表时间：
2023-11-07
影响因子：
3.5
通讯作者：
Chen，Wei
中科院分区：
文献类型：
--
作者：
Zhang，Wen;Li，Yu Jia;Chen，Wei
目的主动脉羧肽酶样蛋白(ACLP)是一种细胞外蛋白，参与脂肪形成、上皮-间充质转化、上皮细胞增殖和胶原纤维形成。本研究旨在分析脂肪细胞增强子结合蛋白1(AEBP1)作为肝纤维化病理靶点或预后标记物的潜在作用，而不考虑病因。方法利用公开的转录图谱、不同的肝纤维化小鼠模型、生物数据库和人肝星状细胞(HSC)中的AEBP1基因沉默和RNA测序，分析AEBP1基因在肝纤维化中的调控模式、临床意义和生物学意义。结果AEBP1基因表达上调，并与肝纤维化的发生呈正相关，其蛋白在不同致病因素诱导的小鼠肝纤维化模型中得到进一步验证。肝AEBP1基因的高表达有可能预测肝纤维化的预后不良。系统的生物信息学分析表明，AEBP1的高表达是HSC特有的，与细胞外基质(ECM)重塑及其下游的机械-化学信号转导有关。AEBP1被特定的小干扰RNA(SiRNAs)敲除后，抑制了ECM-受体的相互作用和免疫相关途径，抑制了HSC的增殖或激活。结论AEBP1的高表达与肝纤维化的发生有关，与预后不良有关，并预测了AEBP1在HSC中的作用，为进一步了解AEBP1在肝纤维化中的作用提供了新的视角。
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 ofAEBP1gene in liver fibrosis were analyzed using publicly available transcriptomic profiles, different liver fibrosis mouse models, biological databases, andAEBP1gene silencing followed by RNA sequencing in human hepatic stellate cells (HSCs).ResultsAEBP1gene 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 liverAEBP1gene had the potential to predict poor prognosis in liver fibrosis. Systematic bioinformatic analyses revealed thatAEBP1expression was HSCs‐specific and associated with extracellular matrix (ECM) remodeling and its downstream mechanical–chemical signaling transition.AEBP1knockdown 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 ofAEBP1was specifically associated with liver fibrosis and was related to a poor prognosis and predicted the role ofAEBP1in HSCs, providing a new insight for understandingAEBP1in liver fibrosis.