Wang Man, Li Lei, Xu Yannan, Du Juan, Ling Changquan
School of Traditional Chinese Medicine, Naval Medical University, Shanghai, China.
Department of Emergency, Changhai Hospital, Naval Medical University, Shanghai, China.
Front Pharmacol. 2022 Oct 13;13:958428. doi: 10.3389/fphar.2022.958428. eCollection 2022.
Non-alcoholic fatty liver disease (NAFLD) has become one of the most common diseases and severe problems worldwide because of the global increase in obesity, dyslipidemia, hypertension, and type 2 diabetes mellitus. NAFLD includes a wide spectrum of liver diseases, the histological forms of which range from non-alcoholic fatty liver (NAFL), which is generally nonprogressive, to non-alcoholic steatohepatitis (NASH), which can progress to chronic hepatitis, liver cirrhosis (LC), and sometimes hepatocellular carcinoma (HCC). Unlike NAFL, as the progressive form of NAFLD, NASH is characterized by the presence of inflammation with or without fibrosis in addition to hepatic steatosis. Although it is widely known and proved that persistent hepatic injury and chronic inflammation in the liver activate quiescent hepatic stellate cells (HSCs) and lead to hepatic fibrosis, the three-step process of "inflammation-fibrosis-carcinoma" in NAFLD has not been investigated and clarified clearly. In this process, the initiation of inflammation in the liver and the function of various liver inflammatory cells have been discussed regularly, while the activated HSCs, which constitute the principal cells responsible for fibrosis and their cross-talk with inflammation, seem not to be investigated specifically and frequently. Also, accumulated evidence suggests that HSCs can not only be activated by inflammation but also participate in the regulation of liver inflammation. Therefore, it is necessary to investigate the unique roles of HSCs in NAFLD from the perspective of inflammation and fibrosis. Here, we review the pivotal effects and mechanisms of HSCs and highlight the potential value of HSC-targeted treatment methods in NAFLD.
由于全球肥胖、血脂异常、高血压和2型糖尿病的发病率上升，非酒精性脂肪性肝病（NAFLD）已成为全球最常见的疾病和严重问题之一。NAFLD包括广泛的肝脏疾病，其组织学形式从通常为非进行性的非酒精性脂肪肝（NAFL）到可进展为慢性肝炎、肝硬化（LC），有时还会发展为肝细胞癌（HCC）的非酒精性脂肪性肝炎（NASH）。与NAFL不同，作为NAFLD的进展形式，NASH的特征除了肝脂肪变性外，还存在有或无纤维化的炎症。尽管众所周知且已证实肝脏中的持续性肝损伤和慢性炎症会激活静止的肝星状细胞（HSC）并导致肝纤维化，但NAFLD中“炎症-纤维化-癌”的三步过程尚未得到明确研究和阐明。在这个过程中，肝脏炎症的起始和各种肝脏炎症细胞的功能经常被讨论，而构成纤维化主要负责细胞的活化HSC及其与炎症的相互作用似乎没有得到专门和频繁的研究。此外，越来越多的证据表明，HSC不仅可以被炎症激活，还参与肝脏炎症的调节。因此，有必要从炎症和纤维化的角度研究HSC在NAFLD中的独特作用。在此，我们综述了HSC的关键作用和机制，并强调了针对HSC的治疗方法在NAFLD中的潜在价值。
