Evidence that Fgf10 offers therapeutic opportunities after hyperoxic lung injury in mice
© Chao et al; licensee Springer 2014
Published: 11 September 2014
Bronchopulmonary dysplasia (BPD), a chronic lung disease of preterm infants, is characterized by impaired alveolar growth and pathologic vascularization.
To investigate the role of Fgf10 in alveologenesis and during/after hyperoxic lung injury.
10 weeks old Fgf10+/- mice (50% Fgf10 expression compared to WT) in normoxic condition: Lung function and morphometric analysis.
Fgf10+ /- and Fgf10 +/+ mice were exposed to 85% O2 from P0-P8. Morphometric analysis and α-Actin/vWF staining were performed at P3.
Rosa26 rtTA/+ ;tet(O)Fgf10 (gain-of-function) mice were exposed to 85% O2 from P0-P8. From P9-P45 the pups were exposed to normoxia and fed either with normal food (control) or doxycycline food (experimental) to activate the transgene Fgf10. Morphometric analysis was carried out at P45.
Tolerance study: Rosa26 rtTA/+ ;tet(O)Fgf10 and WT mice (both 10 weeks old) were exposed to doxycycline for 2 weeks. Then survival rate, histology, Ki67 and TUNEL staining were performed.
Fgf10 +/- mice under normoxic condition have worse lung function and lung structure compared to WT mice.
All Fgf10 +/- mice die from hyperoxic injury due to increased lung injury and vascular malformation.
Overexpression of Fgf10 after hyperoxic injury leads to improvement of lung structure compared to control group without overexpression.
Fgf10 overexpression after hyperoxic injury does not increase mortality and side effects (weight loss, mucosal proliferation due to hypercellularity with no impact on apoptosis) are reversible.
Fgf10 attenuates hyperoxic lung injury, is well tolerated and should be further studied as a potential therapeutic for BPD.
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