Pulmonary Epithelial Neuropilin-1 Deletion Enhances Development of Cigarette Smoke–induced Emphysema

Cigarette smoke exposure aggravates air space enlargement and alveolar cell apoptosis inSmad3knockout mice

“…Increasing evidence suggests that apoptosis of alveolar wall cells plays a critical role in the pathobiology of emphysema (20, 21, 31, 51). A number of studies have linked several signaling pathways with importance for lung development and adult lung homeostasis to emphysema through postnatal lung structure abnormalities and increased apoptosis of alveolar wall cells (8,21,23,34,44). We have previously shown that knockout of the TGF-␤ signaling molecule Smad3 in mice results in postnatal development of air space enlargement.…”

“…Several studies have established a link between impaired signaling pathways, postnatal lung structure abnormalities, and increased apoptosis of alveolar wall cells. In emphysema, this is frequently associated with impairment of VEGF gene expression and VEGF-related signaling (8,20,21,23,31,34,44,50). In addition, autoimmune processes involving autoantibodies and specific lymphocytes have been implicated in alveolar cell apoptosis and emphysema (11,(45)(46)(47).…”

Stress Responses Affecting Homeostasis of the Alveolar Capillary Unit

“…Notwithstanding the evidence that type II cell apoptosis might also occur in emphysema (44), endothelial cells might represent the key cell driving the pathogenesis of destructive airspace enlargement. This interpretation might be supported by the evidence that type II cell apoptosis seen in other lung disease processes, such as acute lung injury (34), are not associated with emphysema development.…”

Involvement of Ceramide in Cell Death Responses in the Pulmonary Circulation

“…vivo with airspace enlargement and a phenotype consistent with lung emphysema (26,38,(57)(58)(59). Exposure to cigarette smoke, which is the most common cause of emphysema, increases ceramides in the human lung, murine lungs, and primary lung endothelial and epithelial cells as well as alveolar macrophages in culture conditions (26,38,39,60,61).…”