Jian Yulun, Li Yuhan, Zhou Yanfeng, Mu Wei
School of Public Health, Center for Single-Cell Omics, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Toxics. 2025 Feb 25;13(3):163. doi: 10.3390/toxics13030163.
This study categorizes pollutant-induced inflammation-cancer transition into three stages: non-alcoholic fatty liver disease (NAFLD), liver fibrosis, and hepatocellular carcinoma (HCC). It systematically reveals the temporal heterogeneity of pollutant-induced liver damage. The findings indicate that pollutants not only directly damage hepatocytes but also modulate key cells in the immune microenvironment, such as hepatic stellate cells (HSCs) and Kupffer cells, thereby amplifying inflammatory and fibrotic responses, ultimately accelerating the progression of HCC. Mechanistically, in the early stage (NAFLD), pollutants primarily cause hepatocyte injury through oxidative stress and lipid metabolism dysregulation. During the fibrosis stage, pollutants promote liver fibrosis by inducing extracellular matrix accumulation, while in the HCC stage, they drive tumorigenesis via activation of the Wnt/β-catenin pathway and p53 inactivation. Through multi-omics analyses, this study identifies critical pathogenic molecules and signaling pathways regulated by pollutants, providing new insights into their pathogenic mechanisms, potential biomarkers, and therapeutic targets. These findings offer valuable guidance for the development of diagnostic and therapeutic strategies for liver diseases and the formulation of environmental health risk prevention measures.
本研究将污染物诱导的炎症-癌症转变分为三个阶段：非酒精性脂肪性肝病（NAFLD）、肝纤维化和肝细胞癌（HCC）。它系统地揭示了污染物诱导的肝损伤的时间异质性。研究结果表明，污染物不仅直接损伤肝细胞，还调节免疫微环境中的关键细胞，如肝星状细胞（HSCs）和库普弗细胞，从而放大炎症和纤维化反应，最终加速HCC的进展。从机制上讲，在早期阶段（NAFLD），污染物主要通过氧化应激和脂质代谢失调导致肝细胞损伤。在纤维化阶段，污染物通过诱导细胞外基质积累促进肝纤维化，而在HCC阶段，它们通过激活Wnt/β-连环蛋白途径和p53失活驱动肿瘤发生。通过多组学分析，本研究确定了受污染物调节的关键致病分子和信号通路，为其致病机制、潜在生物标志物和治疗靶点提供了新的见解。这些发现为肝病诊断和治疗策略的制定以及环境卫生风险预防措施的制定提供了有价值的指导。
