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

详细信息    查看全文

• 作者：Ze Zheng¹ ; Xuebao Zhang¹ ; Jiemei Wang¹ ; Aditya Dandekar² ; Hyunbae Kim¹ ; Yining Qiu¹ ; Xiaohua Xu⁴ ; Yuqi Cui³ ; Aixia Wang³ ; ⁴ ; Lung Chi Chen⁵ ; Sanjay Rajagopalan³ ; ^&dagger ; ; Qinghua Sun³ ; ⁴ ; Kezhong Zhang¹ ; ² ; ^{kzhang@med.wayne.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：PM ; ambient particulate matter ; PM2.5 ; PM with aerodynamic diameter less than 2.5  ; μm ; FA ; filtered air ; OASIS ; Ohio&rsquo ; s Air Pollution Exposure System for the Interrogation of Systemic Effects ; PPAR ; peroxisome proliferator-activated receptor ; TGFβ ; transforming growth factor β ; HSC ; hepatic stellate cells ; p47phox ; Neutrophil cytosolic factor 1 ; NOX ; NADPH peroxidase ; ROS ; reactive oxygen species
• 刊名：Journal of Hepatology
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：63
• 期：6
• 页码：1397-1404
• 全文大小：1721 K

文摘

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 (PM_2.5) correlates with pulmonary dysfunction, cardiovascular disease, and metabolic syndrome. In this study, we investigated the effect and mechanism of PM_2.5 exposure on hepatic fibrogenesis.

Methods

Both inhalation exposure of mice and in vitro exposure of specialized cells to PM_2.5 were performed to elucidate the effect of PM_2.5 exposure on hepatic fibrosis. Histological examinations, gene expression analyses, and genetic animal models were utilized to determine the effect and mechanism by which PM_2.5 exposure promotes hepatic fibrosis.

Results

Inhalation exposure to concentrated ambient PM_2.5 induces hepatic fibrosis in mice under the normal chow or high-fat diet. Mice after PM_2.5 exposure displayed increased expression of collagens in liver tissues. Exposure to PM_2.5 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 PM_2.5-induced liver fibrogenesis.

Conclusions

Exposure to PM_2.5 exerts discernible effects on promoting hepatic fibrogenesis. NADPH oxidase mediates the effects of PM_2.5 exposure on promoting hepatic fibrosis.