چکیده (انگلیسی):

Background: Angiogenesis in the alveolar septa is thought be a critical factor in pulmonary emphysema.
Angiomotin-like protein 1 (AmotL1) is involved in angiogenesis via regulating endothelial cell function. However,
the role of AmotL1 in the pathogenesis of pulmonary emphysema has not been elucidated. The objective
of this study is to evaluate the expression of AmotL1 in lung tissues from a murine model with emphysema, as
well as from patients with chronic obstructive pulmonary disease (COPD). Furthermore, we analyzed the regulation
of AmotL1 expression by TNF-α and IFN-γ in endothelial cells in vitro.
Methods: Nrf2 knockout mice were exposed to cigarette smoke (CS) for 4 weeks, and the down-regulated
genes affecting vascularity in the whole lung were identified by microarray analysis. This analysis revealed that
the mRNA expression of AmotL1 decreased in response to CS when compared with air exposure. To confirm
the protein levels that were indicated in the microarray data, we determined the expression of AmotL1 in lung
tissues obtained from patients with COPD and also determined the expression of AmotL1, NFκB and IκBα in
cultured normal human lung microvascular endothelial cells (HLMVECs) that were stimulated by TNF-α and
IFN-γ.
Results: We found that the number of AmotL1-positive vessels decreased in the emphysema lungs compared
with the normal and bronchial asthmatic lungs. IFN-γ pretreatment diminished the TNF-α-induced AmotL1 in
the cultured HLMVECs by blocking the degradation of IκBα.
Conclusions: These results suggested that IFN-γ exhibits anti-angiogenesis effects by regulating the expression
of TNF-α-induced AmotL1 via NFκB in emphysema lungs.