Exposure to fine airborne particulate matters induces hepatic fibrosis in murine models. J Hepatol 2015 Dec;63(6):1397-404
Date
07/30/2015Pubmed ID
26220751Pubmed Central ID
PMC5003300DOI
10.1016/j.jhep.2015.07.020Scopus ID
2-s2.0-84951567255 (requires institutional sign-in at Scopus site) 138 CitationsAbstract
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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: Exposure to PM2.5 exerts discernible effects on promoting hepatic fibrogenesis. NADPH oxidase mediates the effects of PM2.5 exposure on promoting hepatic fibrosis.
Author List
Zheng Z, Zhang X, Wang J, Dandekar A, Kim H, Qiu Y, Xu X, Cui Y, Wang A, Chen LC, Rajagopalan S, Sun Q, Zhang KAuthor
Ze Zheng PhD Assistant Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCollagen
Hepatic Stellate Cells
Inhalation Exposure
Kupffer Cells
Liver Cirrhosis, Experimental
Male
Mice
Mice, Inbred C57BL
NADPH Oxidases
PPAR gamma
Particulate Matter
Signal Transduction
Transforming Growth Factor beta