Project title
胎盤生長因子於慢性阻塞性肺病成因的角色 (III)
Internal ID
NHRI-EX103-10150SI
Principal Investigator
Start Date
January 1, 2014
End Date
December 31, 2014
Organizations
Partner Organizations
National Health Research Institutes
The Role of Placental Growth Factor in Chronic Obstructive Pulmonary Disease (III) = 胎盤生長因子於慢性阻塞性肺病成因的角色 (III)
Keywords
chronic obstructive pulmonary disease
placental growth factor
elastase
apoptosis
autophagy
Description
Our preliminary data have demonstrated the elevation of placental growth factor (PlGF) in patients with chronic obstructive pulmonary disease (COPD). In addition, animal models with PlGF overexpression and PlGF knockout mice have demonstrated the participation of PlGF in elastaseinduced emphysema mouse model. The central hypothesis of this application is that respiratory tract epithelium is responsible for PlGF production in response to elastase and/or smoke exposure, and this induction is essential for the pathogenesis of emphysema/COPD development. To elucidate the hypothesis, four Specific Aims are proposed. Specific aim 1 is to test whether or not mouse respiratory epithelial cells are responsible for PlGF production in response to elastase treatment. Specific aim 2 is to test whether or not if elastase-induced PlGF is involved in the pathogenesis of mouse emphysema, using both wild-type and PlGF KO mice for the study. Specific Aim 3 is to test whether or not human respiratory epithelial cells are responsible for the elevated PlGF production in patients of COPD and this elevation is correlated with the presence of apoptotic cells in these human lungs. Specific Aim 4 is to test in vitro if PlGF is induced in human respiratory epithelial cells in response to smoke and/or elastase treatment. These studies with a combination of human and mouse in vivo and in vitro models will provide the mechanistic basis on how PlGF is induced and participated in emphysema. The outcome of such a study can also serve as the therapeutic basis for the treatment of COPD patients on targeting PlGF reduction and its mediated signaling.