Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India.
Biochim Biophys Acta Mol Basis Dis. 2024 Apr;1870(4):167102. doi: 10.1016/j.bbadis.2024.167102. Epub 2024 Feb 28.
Non-alcoholic steatohepatitis (NASH) is a pathogenic stage of the broader non-alcoholic fatty liver disease (NAFLD). Histological presentation of NASH includes hepatocyte ballooning, macrophage polarization, ductular reaction, and hepatic stellate cell (HSCs) activation. At a cellular level, a heterogenous population of cells such as hepatocytes, macrophages, cholangiocytes, and HSCs undergo dramatic intra-cellular changes in response to extracellular triggers, which are termed "cellular plasticity. This dynamic switch in the cellular structure and function of hepatic parenchymal and non-parenchymal cells and their crosstalk culminates in the perpetuation of inflammation and fibrosis in NASH. This review presents an overview of our current understanding of cellular plasticity in NASH and its molecular mechanisms, along with possible targeting to develop cell-specific NASH therapies.
非酒精性脂肪性肝炎(NASH)是更为广义的非酒精性脂肪性肝病(NAFLD)的一个致病阶段。NASH 的组织学表现包括肝细胞气球样变、巨噬细胞极化、胆管反应和肝星状细胞(HSCs)激活。在细胞水平上,肝细胞、巨噬细胞、胆管细胞和 HSCs 等异质细胞群会对细胞外刺激发生剧烈的细胞内变化,这被称为“细胞可塑性”。肝实质细胞和非实质细胞的细胞结构和功能的这种动态转换,以及它们的串扰,最终导致 NASH 中的炎症和纤维化持续存在。本综述介绍了我们目前对 NASH 中细胞可塑性及其分子机制的理解,以及可能的靶向治疗以开发针对特定细胞的 NASH 疗法。
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