Exposure to fine airborne particulate matters induces hepatic fibrosis in murine models.

Abstract

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.

• Authors: Ze Zheng, Xuebao Zhang, Jiemei Wang, Aditya Dandekar, Hyunbae Kim, Yining Qiu, Xiaohua Xu, Yuqi Cui, Aixia Wang, Lung Chi Chen, Sanjay Rajagopalan, Qinghua Sun, Kezhong Zhang
• Journal: Journal of hepatology (J Hepatol) Vol. 63 Issue 6 Pg. 1397-404 (Dec 2015) ISSN: 1600-0641 [Electronic] Netherlands
• PMID: 26220751 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015. Published by Elsevier B.V.

Chemical References

• PPAR gamma
• Particulate Matter
• Transforming Growth Factor beta
• Collagen
• NADPH Oxidases

Topics

• Animals
• Collagen (biosynthesis)
• Hepatic Stellate Cells (metabolism)
• Inhalation Exposure
• Kupffer Cells (metabolism)
• Liver Cirrhosis, Experimental (etiology, metabolism, pathology)
• Male
• Mice
• Mice, Inbred C57BL
• NADPH Oxidases (metabolism)
• PPAR gamma (metabolism)
• Particulate Matter (administration & dosage, chemistry, toxicity)
• Signal Transduction
• Transforming Growth Factor beta (metabolism)