Combination effects of airborne particulate matter exposure and high-fat diet on hepatic fibrosis through regulating the ROS-endoplasmic reticulum stress-TGFβ/SMADs axis in mice

Abstract

BackgroundHepatic fibrosis, characterized by an excessive accumulation of extracellular matrix, is associated with toxic substance exposure, chronic infections, mechanical injury, airborne fine particulate matter (PM2.5) exposure and metabolic disease. This study aimed to investigate the effect and mechanism of long-term, real-world airborne particulate matter (PM) exposure on hepatic fibrosis and further explored whether combination treatment of PM exposure and high-fat diet (HFD) aggravate the adverse effects in mice. Methods and resultsSix-week-old male C57BL/6J mice fed with either a standard chow diet (STD) or an HFD were treated with either filtered air (FA) or PM for 18 weeks. Metabolic parameters, histological examination, gene expression analysis, and Western blot analysis were utilized to measure the effect and mechanism of PM exposure on hepatic fibrosis and to further analyze the synergistic effect of HFD. Subchronic airborne PM exposure induces hepatic fibrosis in mice, and combination treatment of PM exposure and HFD accelerate the adverse effect. Meanwhile, subchronic exposure to real-world PM increased the level of hepatic ROS, and the expression of endoplasmic reticulum (ER) stress markers (GRP78 and CHOP), p-SMAD2 and p-SMAD3, as well as up-regulated TGFβ and collagen 1 in liver tissues. Furthermore, PM exposure and HFD displayed the synergistic effects on these changes in liver. ConclusionOur findings indicate that airborne PM exposure aggravates HFD -induced hepatic fibrosis. The ROS-ER stress-TGFβ/SMADs regulatory axis mediates the effects of airborne PM exposure on accelerating hepatic fibrosis.