Notch1 regulates endothelial apoptosis via ERK pathway in chronic obstructive pulmonary disease

Notch signaling is a critical cell fate determinant of proliferation, differentiation, and apoptosis. In this current study we aimed to investigate whether Notch signaling is involved in cigarette smoke (CS) induced endothelial apoptosis in COPD. Surgical specimens were obtained from 10 patients with COPD and 10 control participants. Notch1, 2, 4 were expressed in endothelial cells, whereas, Notch3 was mainly localized in smooth muscle cells. Decreased Notch1, 3, 4 and the target gene Hes1 and Hes2, increased Notch2 and extracellular signal-regulated kinase (ERK)1/2 were found in COPD patients compared with controls, as well as in human pulmonary microvascular endothelial cells (HPMECs) when exposed to CS extract (CSE). Over-expression of Notch1 with N1ICD markedly alleviated the apoptosis induced by CSE. ERK pathway was significantly activated by CSE, which was positively correlated with CSE induced apoptosis. However, this activation can be abolished by N1ICD over-expression. Furthermore, PD98059 (ERK i...