缺氧诱导因子1α(HIF-1α)/Yes相关蛋白(YAP)在非酒精性脂肪性肝病中的调控作用

Regulatory role of hypoxia-inducible factor-1α/Yes-associated protein in nonalcoholic fatty liver disease

非酒精性脂肪性肝病(NAFLD)是目前最为常见的慢性肝病,并与多种代谢性疾病密切相关,如2型糖尿病、胰岛素抵抗,以及与高血压和血脂异常相关的心脑血管并发症。NAFLD病因和病理机制复杂,微环境因素和基因表达调节异常存在于疾病进展的各个阶段,并通过累加效应促进疾病发展。缺氧诱导因子(HIF)是核转录因子、Yes相关蛋白(YAP)是转录辅助调节因子,二者通过调节肝脂质沉积与氧化应激,促进炎性因子释放,与NAFLD进展密切相关。本文对HIF-1α/YAP在NAFLD及其相关代谢性疾病进展中的作用进行综述,为探索NAFLD疾病进展过程中的相关治疗靶点提供理论依据。

Nonalcoholic fatty liver disease(NAFLD)is the most common chronic liver disease in the world and is closely associated with a variety of metabolic diseases,such as type 2 diabetes,insulin resistance,and cardiovascular and cerebrovascular complications associated with hypertension and dyslipidemia.NAFLD has complex etiologies and pathological mechanisms,and abnormal microenvironmental factors and gene expression regulation exist in all stages of disease progression and promote disease progression through cumulative effects.Hypoxia-inducible factors are hypoxia-inducible transcription factors,and Yes-associated protein(YAP)/transcriptional coactivator with PDZ-binding motif is a transcriptional coactivator,both of which are closely associated with the progression of NAFLD by regulating lipid deposition and oxidative stress in the liver and promoting the release of inflammatory factors.This article reviews the role of hypoxia-inducible factor-1α/YAP in the progression of NAFLD and its related metabolic diseases,so as to provide a theoretical basis for related therapeutic targets in the progression of NAFLD.