Dataset Information

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

ABSTRACT: 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 ?-SMAD3 signaling, suppression of peroxisome proliferator-activated receptor ?, 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.

SUBMITTER: Zheng Z

PROVIDER: S-EPMC5003300 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Zheng Ze Z Zhang Xuebao X Wang Jiemei J Dandekar Aditya A Kim Hyunbae H Qiu Yining Y Xu Xiaohua X Cui Yuqi Y Wang Aixia A Chen Lung Chi LC Rajagopalan Sanjay S Sun Qinghua Q Zhang Kezhong K

Journal of hepatology 20150726 6

<h4>Background & aims</h4>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.<h4>Methods</h4>Both inhalation exposure of mice and in vitro exposu ...[more]

PMID: 26220751

Similar Datasets

Project description:BACKGROUND:Cardiovascular disease is the leading cause of mortality in the advanced world, and age is an important determinant of cardiac function. The purpose of the study is to determine whether the PM2.5-induced cardiac dysfunction is age-dependent and whether the adverse effects can be restored after PM2.5 exposure withdrawal. METHODS:Female C57BL/6 mice at different ages (4-week-old, 4-month-old, and 10-month-old) received oropharyngeal aspiration of 3 mg/kg b.w. PM2.5 every other day for 4 weeks. Then, 10-month-old and 4-week-old mice were exposed to PM2.5 for 4 weeks and withdrawal PM2.5 1 or 2 weeks. Heart rate and systolic blood pressure were measured using a tail-cuff system. Cardiac function was assessed by echocardiography. Left ventricles were processed for histology to assess myocardial fibrosis. ROS generation was detected by photocatalysis using 2',7'-dichlorodihydrofluorescein diacetate (DCFHDA). The expression of cardiac fibrosis markers (Col1a1, Col3a1) and possible signaling molecules, including NADPH oxidase 4 (NOX-4), transforming growth factor ?1 (TGF?1), and Smad3, were detected by qPCR and/ or Western blot. RESULTS:PM2.5 exposure induced cardiac diastolic dysfunction of mice, elevated the heart rate and blood pressure, developed cardiac systolic dysfunction of 10-month-old mice, and caused fibrosis in both 4-week-old and 10-month-old mice. PM2.5 exposure increased the expression of Col1a1, Col3a1, NOX-4, and TGF?1, activated Smad3, and generated more reactive oxygen species in the myocardium of 4-week-old and 10-month-old mice. The withdrawal from PM2.5 exposure restored blood pressure, heart rate, cardiac function, expression of collagens, and malonaldehyde (MDA) levels in hearts of both 10-month-old and 4-week-old mice. CONCLUSION:Juvenile and older mice are more sensitive to PM2.5 than adults and suffer from cardiac dysfunction. PM2.5 exposure reversibly elevated heart rate and blood pressure, induced cardiac systolic dysfunction of older mice, and reversibly induced fibrosis in juvenile and older mice. The mechanism by which PM2.5 exposure resulted in cardiac lesions might involve oxidative stress, NADPH oxidase, TGF?1, and Smad-dependent pathways.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets