空气污染与肝脏疾病

A research team led by Kezhong Zhang, Ph.D., at the Wayne State University School of Medicine's Center for Molecular ¹ Medicine and Genetics, has discovered that exposure to air pollution has a direct adverse ² health effect on the liver and causes liver fibrosis, an illness associated with metabolic ³ disease and liver cancer. Dr. Zhang, assistant professor of Molecular Medicine and Genetics and of Immunology and Microbiology, and his group have been studying the adverse health effects of air pollution from a unique perspective. While the major research efforts in the field were focused on the effects of air pollution on lung tissues and cardiovascular system, the Zhang lab studied the pathological effects and stress mechanisms ⁴ of air pollution on the liver, the major organ of detoxification and metabolism ⁵. Their work demonstrated that inhalation exposure to high-concentration airborne particulate ⁶ matter PM2.5 has direct effects on the liver, triggering liver fibrosis, a pathological condition characterized by accumulation of the extracellular matrix protein collagen that occurs in most types of chronic ⁸ liver diseases., ,PM2.5 is fine airborne particulate matter with aerodynamic diameter smaller than 2.5 micrometers. It is a complex mixture of particles and gases from gasoline and diesel ⁹ engines, together with dust from wear of road surfaces, tires and brakes. PM2.5 is the major and most toxic ¹⁰ component ¹¹ of air pollutants ¹² in the real-world air environment of intensive traffic or industrial activity. Recent epidemiological studies confirmed that populations exposed to high-level PM2.5 are at a higher risk of developing heart disease and metabolic disease., ,Dr. Zhang said that PM2.5 pollution has major impact on the public health for the general population in urban areas, such as Detroit, one of the most PM2.5-polluted cities in the United States, according to annual air quality reports by the American Lung Association., ,Dr. Zhang's group, in collaboration ¹³ with a research group at the Ohio State University College of Public Health led by Qinghua Sun, M.D., Ph.D., professor and assistant dean for Global Public Health, performed both short-time and long-term inhalation exposure of animal models to real-world PM2.5. After a 10-week exposure, the animals developed liver fibrosis. Utilizing ¹⁴ molecular, cellular ⁷ and pathological approaches, the team discovered the stress sensor ¹⁵ on the cell membrane ¹⁶ that initiates ¹⁷ PM2.5-triggered stress signals and the mediators inside the cell that transduces the signaling. The PM2.5-triggered inflammatory stress responses promote collagen deposition ¹⁸ -- a hallmark of fibrosis -- in the liver through activating ¹⁹ the transforming growth factor β (TGFβ) signaling. This work will soon be published in the Journal of Hepatology.