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Updated: Mar 20, 2026
Mouse Pneumonectomy Model of Compensatory Lung Growth
Published on: December 17, 2014
Downregulation of pigment epithelium-derived factor increases compensatory lung growth in mice after extended
Thomas I Hirsch1,2, Savas T Tsikis1,2, Djanira Fernandes1,2
1Vascular Biology Program, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Background:
Pulmonary hypoplasia following lung resection for congenital conditions (lobar emphysema or sequestration) may involve significant tissue loss. Previously, our lab demonstrated that FG-4592, a prolyl hydroxylase inhibitor, accelerates murine compensatory lung growth (CLG) following left pneumonectomy (LP). In this study, we investigated FG-4592 in a more severe disease model involving removal of both the left lung and right caval lobe (extended pneumonectomy; EP) which is characterized by decreased CLG.
Methods:
EP was performed in mice, followed by treatment with FG-4592. Lung regeneration was assessed at postoperative day (POD) 8 and 14 using pulmonary function tests, exercise tolerance testing, histologic analysis of alveolarization and angiogenesis. Pigment epithelium-derived factor (PEDF) knockout mice were used to explore the mechanism of FG-4592-induced angiogenesis.
Results:
FG-4592 treatment significantly improved lung function and exercise tolerance at POD 8, with sustained benefits observed at POD 14. Enhanced alveolarization and angiogenesis were noted. Experiments utilizing PEDF knockout mice confirmed that FG-4592-induced angiogenesis is driven by PEDF downregulation.
Conclusion:
FG-4592 increases lung regeneration following EP by promoting alveolar and vascular growth, mediated in part by PEDF downregulation. These findings support FG-4592 as a potential therapeutic candidate in conditions where CLG is required for recovery of lung function.
Impact:
FG-4592 increases lung function and growth in a murine model of severe compensatory lung growth The current study expands on our understanding of FG-4592 and establishes its efficacy in a more severe model than previously tested FG-4592 increases angiogenic signaling through the vascular endothelial growth factor receptor 2, a pathway that is important in lung growth and development FG-4592 is expected to have efficacy in both male and female pediatric patients with severe pulmonary hypoplasia after lung resection.
