tailieunhanh - Báo cáo y học: "Cigarette smoke regulates VEGFR2-mediated survival signaling in rat lungs"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: Cigarette smoke regulates VEGFR2-mediated survival signaling in rat lungs. | Marwick et al. Journal of Inflammation 2010 7 11 http content 7 1 11 JOURNAL OF INFLAMMATION RESEARCH Open Access Cigarette smoke regulates VEGFR2-mediated survival signaling in rat lungs John A Marwick1 2 Indika Edirisinghe 4 Gnanapragasam Arunachalam4 Christopher S Stevenson1 2 William MacNee3 Paul A Kirkham1 2 Irfan Rahman4 Abstract Background Vascular endothelial growth factor VEGF and VEGF receptor 2 VEGFR2 -mediated survival signaling is critical to endothelial cell survival maintenance of the vasculature and alveolar structure and regeneration of lung tissue. Reduced VEGF and VEGFR2 expression in emphysematous lungs has been linked to increased endothelial cell death and vascular regression. Previously we have shown that CS down-regulated the VEGFR2 and its downstream signaling in mouse lungs. However the VEGFR2-mediated survival signaling in response to oxidants cigarette smoke CS is not known. We hypothesized that CS exposure leads to disruption of VEGFR2-mediated endothelial survival signaling in rat lungs. Methods Adult male Sprague-Dawley rats were exposed CS for 3 days 8 weeks and 6 months to investigate the effect of CS on VEGFR2-mediated survival signaling by measuring the Akt PI3-kinase eNOS downstream signaling in rat lungs. Results and Discussion We show that CS disrupts VEGFR2 PI3-kinase association leading to decreased Akt and eNOS phosphorylation. This may further alter the phosphorylation of the pro-apoptotic protein Bad and increase the Bad Bcl-xl association. However this was not associated with a significant lung cell death as evidenced by active caspase-3 levels. These data suggest that although CS altered the VEGFR2-mediated survival signaling in the rat lungs but it was not sufficient to cause lung cell death. Conclusion The rat lungs exposed to CS in acute sub-chronic and chronic levels may be representative of smokers where survival signaling is altered but was not associated with lung cell death whereas .