Zheng Ze, Zhang Xuebao, Wang Jiemei, Dandekar Aditya, Kim Hyunbae, Qiu Yining, Xu Xiaohua, Cui Yuqi, Wang Aixia, Chen Lung Chi, Rajagopalan Sanjay, Sun Qinghua, Zhang Kezhong
Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
J Hepatol. 2015 Dec;63(6):1397-404. doi: 10.1016/j.jhep.2015.07.020. Epub 2015 Jul 26.
BACKGROUND & AIMS: Hepatic fibrosis, featured by the accumulation of excessive extracellular matrix in liver tissue, is associated with metabolic disease and cancer. Inhalation exposure to airborne particulate matter in fine ranges (PM2.5) correlates with pulmonary dysfunction, cardiovascular disease, and metabolic syndrome. In this study, we investigated the effect and mechanism of PM2.5 exposure on hepatic fibrogenesis.
Both inhalation exposure of mice and in vitro exposure of specialized cells to PM2.5 were performed to elucidate the effect of PM2.5 exposure on hepatic fibrosis. Histological examinations, gene expression analyses, and genetic animal models were utilized to determine the effect and mechanism by which PM2.5 exposure promotes hepatic fibrosis.
Inhalation exposure to concentrated ambient PM2.5 induces hepatic fibrosis in mice under the normal chow or high-fat diet. Mice after PM2.5 exposure displayed increased expression of collagens in liver tissues. Exposure to PM2.5 led to activation of the transforming growth factor β-SMAD3 signaling, suppression of peroxisome proliferator-activated receptor γ, and expression of collagens in hepatic stellate cells. NADPH oxidase plays a critical role in PM2.5-induced liver fibrogenesis.
Exposure to PM2.5 exerts discernible effects on promoting hepatic fibrogenesis. NADPH oxidase mediates the effects of PM2.5 exposure on promoting hepatic fibrosis.
肝纤维化以肝组织中细胞外基质过度积聚为特征,与代谢性疾病和癌症相关。吸入细颗粒物(PM2.5)与肺功能障碍、心血管疾病和代谢综合征相关。在本研究中,我们调查了PM2.5暴露对肝纤维化的影响及其机制。
对小鼠进行吸入暴露,对特定细胞进行体外暴露,以阐明PM2.5暴露对肝纤维化的影响。利用组织学检查、基因表达分析和基因动物模型来确定PM2.5暴露促进肝纤维化的作用和机制。
在正常饮食或高脂饮食条件下,吸入浓缩环境PM2.5可诱导小鼠肝纤维化。PM2.5暴露后的小鼠肝脏组织中胶原蛋白表达增加。暴露于PM2.5导致转化生长因子β-SMAD3信号通路激活、过氧化物酶体增殖物激活受体γ受抑制以及肝星状细胞中胶原蛋白表达。NADPH氧化酶在PM2.5诱导的肝纤维化中起关键作用。
暴露于PM2.5对促进肝纤维化有明显影响。NADPH氧化酶介导PM2.5暴露促进肝纤维化的作用。