Overexpression of Placenta Growth Factor Contributes to the Pathogenesis of Pulmonary Emphysema

Po Nien Tsao, Yi Ning Su, Hung Li, Pei Hsin Huang, Chiang Ting Chien, Yih Loong Lai, Chien Nan Lee, Chi An Chen, Wen Fang Cheng, Shu Chen Wei, Chong Jen Yu, Fon Jou Hsieh, Su Ming Hsu

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73 Citations (Scopus)

Abstract

To examine the role of placenta growth factor (PIGF) in the pathogenesis of pulmonary emphysema, we generated PIGF-transgenic (TG) mice using a phosphoglycerate kinase promoter. This resulted in constitutive overexpression of PIGF. 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 PIGF can inhibit the proliferation and promote the cell death of mouse type II pneumocytes. In normal newborn mice, abundant expression of PIGF messenger RNA was detected in the lungs during saccular division but was rapidly downregulated after alveolarization was complete. Thus, a persistently elevated PIGF was detrimental to the developed lung and causes the emphysematous change seen in our TG mice. Our study suggests that PIGF plays an important role in the pathogenesis of pulmonary emphysema via its action on type II pneumocytes.

Original languageEnglish
Pages (from-to)505-511
Number of pages7
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume169
Issue number4
DOIs
Publication statusPublished - 2004 Feb 15

Keywords

  • Placenta growth factor
  • Pulmonary emphysema
  • Transgenic mice

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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    Tsao, P. N., Su, Y. N., Li, H., Huang, P. H., Chien, C. T., Lai, Y. L., Lee, C. N., Chen, C. A., Cheng, W. F., Wei, S. C., Yu, C. J., Hsieh, F. J., & Hsu, S. M. (2004). Overexpression of Placenta Growth Factor Contributes to the Pathogenesis of Pulmonary Emphysema. American Journal of Respiratory and Critical Care Medicine, 169(4), 505-511. https://doi.org/10.1164/rccm.200306-774oc