title: Overexpression of placenta growth factor contributes to the pathogenesis of pulmonary emphysema.
abstract: To examine the role of placenta growth factor (PlGF) in the pathogenesis of pulmonary emphysema, we generated PlGF-transgenic (TG) mice using a phosphoglycerate kinase promoter. This resulted in constitutive overexpression of PlGF. In these TG mice, pulmonary emphysema, with enlarged air spaces and enhanced pulmonary compliance, first appeared at 6 months of age and became prominent at 12 months. Increased alveolar septal cell apoptosis was noted in their lungs. Fluorescence-activated cell sorter analysis suggests that these apoptotic septal cells are type II pneumocytes. At the same time, the messenger RNA of vascular endothelial growth factor and platelet-endothelial cell adhesion molecule-1, an endothelial cell marker, were downregulated indicating a reduced number of endothelial cells and its survival factor VEGF. In vitro, exogenous PlGF can inhibit the proliferation and promote the cell death of mouse type II pneumocytes. In normal newborn mice, abundant expression of PlGF messenger RNA was detected in the lungs during saccular division but was rapidly downregulated after alveolarization was complete. Thus, a persistently elevated PlGF was detrimental to the developed lung and causes the emphysematous change seen in our TG mice. Our study suggests that PlGF plays an important role in the pathogenesis of pulmonary emphysema via its action on type II pneumocytes.
authors.affiliation: Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan, Republic of China.
authors.forename: Po-Nien
authors.initials: PN
authors.lastname: Tsao
authors.forename: Yi-Ning
authors.initials: YN
authors.lastname: Su
authors.forename: Hung
authors.initials: H
authors.lastname: Li
authors.forename: Pei-Hsin
authors.initials: PH
authors.lastname: Huang
authors.forename: Chiang-Ting
authors.initials: CT
authors.lastname: Chien
authors.forename: Yih-Loong
authors.initials: YL
authors.lastname: Lai
authors.forename: Chien-Nan
authors.initials: CN
authors.lastname: Lee
authors.forename: Chi-An
authors.initials: CA
authors.lastname: Chen
authors.forename: Wen-Fang
authors.initials: WF
authors.lastname: Cheng
authors.forename: Shu-Chen
authors.initials: SC
authors.lastname: Wei
authors.forename: Chong-Jen
authors.initials: CJ
authors.lastname: Yu
authors.forename: Fon-Jou
authors.initials: FJ
authors.lastname: Hsieh
authors.forename: Su-Ming
authors.initials: SM
authors.lastname: Hsu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006133:Growth Substances / Q000502:physiology*; D007091:Image Processing, Computer-Assisted; D020287:In Situ Nick-End Labeling; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D018995:Myosin Heavy Chains; D024501:Nonmuscle Myosin Type IIB; D000072483:Placenta Growth Factor; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011257:Pregnancy Proteins / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D011650:Pulmonary Alveoli / Q000254:growth & development / Q000473:pathology; D011656:Pulmonary Emphysema / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D016326:Extracellular Matrix Proteins; D006133:Growth Substances; C000608037:Pgf protein, mouse; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011257:Pregnancy Proteins; D042461:Vascular Endothelial Growth Factor A; D000072483:Placenta Growth Factor; D024501:Nonmuscle Myosin Type IIB; C103815:nonmuscle myosin type IIB heavy chain; D018995:Myosin Heavy Chains