Proliferative activity of liver growth factor is associated with an improvement of cigarette smoke-induced emphysema in mice

• Published in: PloS one Vol. 9; no. 11; p. e112995
• Main Authors: Girón-Martínez, Álvaro, Pérez-Rial, Sandra, Terrón-Expósito, Raúl, Díaz-Gil, Juan José, González-Mangado, Nicolás, Peces-Barba, Germán
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 17-11-2014; Public Library of Science (PLoS)
• Subjects: Alveoli; Animal models; Animals; Antioxidants; Bilirubin; Bilirubin - administration & dosage; Bilirubin - pharmacology; Biology and Life Sciences; Body Weight; Bronchodilators; Cell proliferation; Chronic obstructive pulmonary disease; Cigarette smoke; Cigarettes; Corticoids; Corticosteroids; Critical care; Disease Models, Animal; Emphysema; Enlargement; Exposure; Health aspects; Hyperoxia; Liver; Liver diseases; Lung diseases; Lungs; Male; Matrix metalloproteinase; Matrix Metalloproteinases - metabolism; Medical research; Medical treatment; Medicine; Medicine and Health Sciences; Metalloproteinase; Mice; Nitrogen; Obstructive lung disease; Oxidative Stress; Physiology; Proliferating cell nuclear antigen; Proliferating Cell Nuclear Antigen - metabolism; Pulmonary Alveoli - pathology; Pulmonary Emphysema - drug therapy; Pulmonary Emphysema - etiology; Pulmonary Emphysema - pathology; Pulmonary Emphysema - physiopathology; Research and Analysis Methods; Respiratory function; Respiratory Function Tests; Respiratory system agents; Rodents; Serum Albumin - administration & dosage; Serum Albumin - pharmacology; Serum Albumin, Human; Smoke; Smoking; Smoking - adverse effects; Stem cells; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - metabolism; Spain
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0112995

Cigarette smoke (CS)-induced emphysema is a major component of chronic obstructive pulmonary disease (COPD). COPD treatment is based on the administration of bronchodilators and corticosteroids to control symptoms and exacerbations, however, to date, there are no effective therapies to reverse disease progression. Liver growth factor (LGF) is an albumin-bilirubin complex with mitogenic properties, whose therapeutic effects have previously been reported in a model of emphysema and several rodent models of human disease. To approach the therapeutic effect of LGF in a model of previously established emphysema, morphometric and lung function parameters, matrix metalloproteinase (MMP) activity and the expression of several markers, such as VEGF, PCNA, 3NT and Nrf2, were assessed in air-exposed and CS-exposed C57BL/6J male mice with and without intraperitoneal (i.p.) injection of LGF. CS-exposed mice presented a significant enlargement of alveolar spaces, higher alveolar internal area and loss of lung function that correlated with higher MMP activity, higher expression of 3NT and lower expression of VEGF. CS-exposed mice injected with LGF, showed an amelioration of emphysema and improved lung function, which correlated with lower MMP activity and 3NT expression and higher levels of VEGF, PCNA and Nrf2. Taken together, this study suggests that LGF administration ameliorates CS-induced emphysema, highlights the ability of LGF to promote alveolar cell proliferation and may be a promising strategy to revert COPD progression.