Han Jinsol, Jeong Hayeong, Lee Chanbin, Sung Ahyeon, Choi Yung Hyun, Jung Youngmi
Institution of Systems Biology, Pusan National University, Pusan, Republic of Korea.
Department of Integrated Biological Science, College of Natural Science, Pusan National University, Pusan, Republic of Korea.
Liver Int. 2025 Aug;45(8):e70224. doi: 10.1111/liv.70224.
Plastic particles are a global pollution problem, and humans are potentially exposed to them. Ingested plastic particles, microparticles (MPs) and nanoparticles (NPs), predominantly accumulate in the liver and cause hepatotoxicity through oxidative stress and metabolic dysfunction. NPs promote more toxic actions than MPs; however, the mechanisms involved in developing and progressing metabolic dysfunction-associated steatotic liver disease (MASLD) from chronic exposure to NPs remain poorly understood. Hedgehog (Hh) signalling regulates MASLD pathogenesis. Herein, we investigated the pathophysiological effects of NPs in MASLD.
Mice were orally administered NPs via drinking water while fed a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) for 12 weeks.
NPs increased lipid accumulation in hepatocytes and apoptosis. Moreover, these actions were enhanced in lipotoxicity-exposed hepatocytes. Chronically exposed NPs accumulated in mice livers and aggravated CDAHFD-induced hepatic damage, especially fibrosis. Activated Hh signalling in the CDAHFD group was elevated by NP treatment. Increased Sonic Hh expression in the hepatocytes of NP-treated mice in the CDAHFD group triggered Hh signalling in hepatic stellate cells (HSCs), which promoted liver fibrosis.
These results demonstrate that chronic exposure to NPs increases vulnerability to MASLD progression, suggesting that NPs are a potentially harmful factor in the development and progression of liver disease.
塑料颗粒是一个全球性的污染问题，人类有可能接触到它们。摄入的塑料颗粒，即微塑料（MPs）和纳米塑料（NPs），主要积聚在肝脏中，并通过氧化应激和代谢功能障碍导致肝毒性。与MPs相比，NPs会引发更多的毒性作用；然而，长期接触NPs导致代谢功能障碍相关脂肪性肝病（MASLD）发生和进展的机制仍知之甚少。刺猬（Hh）信号通路调节MASLD的发病机制。在此，我们研究了NPs在MASLD中的病理生理作用。
给小鼠经饮水口服NPs，同时喂以胆碱缺乏、L-氨基酸限定的高脂饮食（CDAHFD），持续12周。
NPs增加了肝细胞中的脂质积累和细胞凋亡。此外，这些作用在暴露于脂毒性的肝细胞中增强。长期接触的NPs在小鼠肝脏中积聚，并加重了CDAHFD诱导的肝损伤，尤其是纤维化。NP处理使CDAHFD组中激活的Hh信号通路增强。CDAHFD组经NP处理的小鼠肝细胞中Sonic Hh表达增加，触发了肝星状细胞（HSCs）中的Hh信号通路，从而促进了肝纤维化。
这些结果表明，长期接触NPs会增加患MASLD进展的易感性，提示NPs是肝脏疾病发生和进展中的一个潜在有害因素。
