epidermal-growth-factor and Emphysema

Multipotent stromal cells (MSCs) ameliorate several types of lung injury. The differentiation of MSCs into specific cells at the injury site has been considered as the important process in the MSC effect. However, although MSCs reduce destruction in an elastase-induced lung emphysema model, MSC differentiation is relatively rare, suggesting that MSC differentiation into specific cells does not adequately explain the recuperation observed. Humoral factors secreted by MSCs may also play an important role in ameliorating emphysema. To confirm this hypothesis, emphysema was induced in the lungs of C57BL/6 mice by intratracheal elastase injection 14 days before intratracheal MSC or phosphate-buffered saline (PBS) administration. Thereafter, lungs were collected at several time points and evaluated. Our results showed that MSCs reduced the destruction in elastase-induced emphysema. Furthermore, double immunofluorescence staining revealed infrequent MSC engraftment and differentiation into epithelial cells. Real-time PCR showed increased levels of hepatocyte growth factor (HGF) and epidermal growth factor (EGF). Real-time PCR and western blotting showed enhanced production of secretory leukocyte protease inhibitor (SLPI) in the lung. In-vitro coculture studies confirmed the in vivo observations. Our findings suggest that paracrine factors derived from MSCs is the main mechanism for the protection of lung tissues from elastase injury.

Topics: Animals; Blotting, Western; Cell Line; Emphysema; Epidermal Growth Factor; Epithelial Cells; Fluorescent Antibody Technique; Hepatocyte Growth Factor; Interleukin-1beta; Mice; Mice, Inbred C57BL; Mice, Knockout; Models, Animal; Multipotent Stem Cells; Pancreatic Elastase; Pulmonary Alveoli; Reverse Transcriptase Polymerase Chain Reaction; Secretory Leukocyte Peptidase Inhibitor; Up-Regulation

Chronic obstructive pulmonary disease (COPD) is a respiratory disease characterized by permanent and progressive airway obstruction. Cigarette smoking is the main cause responsible for COPD although only 15 to 25 % of smokers develop COPD. Mechanisms underlying COPD pathogenesis are not fully understood. Structural abnormalities in small airways (bronchioles < 2mm in diameter) are the main determinants of airway obstruction; obstruction of these bronchioles is related to increase in airway wall thickness (associated with peribronchiolar fibrosis) and to plugging by mucus exudates. Alveolar wall destruction (emphysema) also contributes to airway obstruction and to gas exchange abnormalities. Current knowledge related to molecular and cellular mechanisms responsible for these structural modifications are reviewed.

Topics: Bronchi; Disease Progression; Emphysema; Epidermal Growth Factor; ErbB Receptors; Humans; Pulmonary Disease, Chronic Obstructive; Pulmonary Fibrosis; Smoking