title: Liver growth factor treatment reverses emphysema previously established in a cigarette smoke exposure mouse model.
abstract: Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease largely associated with cigarette smoke exposure (CSE) and characterized by pulmonary and extrapulmonary manifestations, including systemic inflammation. Liver growth factor (LGF) is an albumin-bilirubin complex with demonstrated antifibrotic, antioxidant, and antihypertensive actions even at extrahepatic sites. We aimed to determine whether short LGF treatment (1.7 μg/mouse ip; 2 times, 2 wk), once the lung damage was established through the chronic CSE, contributes to improvement of the regeneration of damaged lung tissue, reducing systemic inflammation. We studied AKR/J mice, divided into three groups: control (air-exposed), CSE (chronic CSE), and CSE + LGF (LGF-treated CSE mice). We assessed pulmonary function, morphometric data, and levels of various systemic inflammatory markers to test the LGF regenerative capacity in this system. Our results revealed that the lungs of the CSE animals showed pulmonary emphysema and inflammation, characterized by increased lung compliance, enlargement of alveolar airspaces, systemic inflammation (circulating leukocytes and serum TNF-α level), and in vivo lung matrix metalloproteinase activity. LGF treatment was able to reverse all these parameters, decreasing total cell count in bronchoalveolar lavage fluid and T-lymphocyte infiltration in peripheral blood observed in emphysematous mice and reversing the decrease in monocytes observed in chronic CSE mice, and tends to reduce the neutrophil population and serum TNF-α level. In conclusion, LGF treatment normalizes the physiological and morphological parameters and levels of various systemic inflammatory biomarkers in a chronic CSE AKR/J model, which may have important pathophysiological and therapeutic implications for subjects with stable COPD.
authors.affiliation: Respiratory Research Group, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz-CIBERES (IIS-FJD-CIBERES), Madrid, Spain sperezr@fjd.es.
authors.forename: Sandra
authors.initials: S
authors.lastname: Pérez-Rial
authors.affiliation: Respiratory Research Group, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz-CIBERES (IIS-FJD-CIBERES), Madrid, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Del Puerto-Nevado
authors.affiliation: Respiratory Research Group, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz-CIBERES (IIS-FJD-CIBERES), Madrid, Spain.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Girón-Martínez
authors.affiliation: Respiratory Research Group, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz-CIBERES (IIS-FJD-CIBERES), Madrid, Spain.
authors.forename: Raúl
authors.initials: R
authors.lastname: Terrón-Expósito
authors.affiliation: Respiratory Research Group, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz-CIBERES (IIS-FJD-CIBERES), Madrid, Spain.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Díaz-Gil
authors.affiliation: Respiratory Research Group, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz-CIBERES (IIS-FJD-CIBERES), Madrid, Spain.
authors.forename: Nicolás
authors.initials: N
authors.lastname: González-Mangado
authors.affiliation: Respiratory Research Group, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz-CIBERES (IIS-FJD-CIBERES), Madrid, Spain.
authors.forename: Germán
authors.initials: G
authors.lastname: Peces-Barba
mesh_terms: D000818:Animals; D001663:Bilirubin / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D002465:Cell Movement / Q000187:drug effects; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006801:Humans; D007274:Injections, Intraperitoneal; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000276:immunology; D051379:Mice; D008806:Mice, Inbred AKR; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000139:chemically induced / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D011656:Pulmonary Emphysema / Q000139:chemically induced / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D012129:Respiratory Function Tests; D012709:Serum Albumin / Q000494:pharmacology*; D000075462:Serum Albumin, Human; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology
chemical_list: D012709:Serum Albumin; D014028:Tobacco Smoke Pollution; D014409:Tumor Necrosis Factor-alpha; C053498:albumin-bilirubin complex; D020782:Matrix Metalloproteinases; D001663:Bilirubin; D000075462:Serum Albumin, Human
keywords: chronic cigarette smoke exposure; emphysema; liver growth factor; mice model; therapy