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Evidence that Fgf10 offers therapeutic opportunities after hyperoxic lung injury in mice

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Bronchopulmonary dysplasia (BPD), a chronic lung disease of preterm infants, is characterized by impaired alveolar growth and pathologic vascularization.

Aims

To investigate the role of Fgf10 in alveologenesis and during/after hyperoxic lung injury.

Methods

  1. 1)

    10 weeks old Fgf10+/- mice (50% Fgf10 expression compared to WT) in normoxic condition: Lung function and morphometric analysis.

  2. 2)

    BPD model:

  3. a)

    Fgf10+ /- and Fgf10+/+ mice were exposed to 85% O2 from P0-P8. Morphometric analysis and α-Actin/vWF staining were performed at P3.

  4. b)

    Rosa26rtTA/+ ;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.

  5. 3)

    Tolerance study: Rosa26rtTA/+ ;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.

Results

  1. 1)

    Fgf10+/- mice under normoxic condition have worse lung function and lung structure compared to WT mice.

  2. 2)

    All Fgf10+/- mice die from hyperoxic injury due to increased lung injury and vascular malformation.

  3. 3)

    Overexpression of Fgf10 after hyperoxic injury leads to improvement of lung structure compared to control group without overexpression.

  4. 4)

    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.

Conclusion

Fgf10 attenuates hyperoxic lung injury, is well tolerated and should be further studied as a potential therapeutic for BPD.

Author information

Correspondence to CM Chao.

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Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0), which permits use, duplication, adaptation, distribution, and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

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Keywords

  • Lung Function
  • Doxycycline
  • Morphometric Analysis
  • Vascular Malformation
  • Chronic Lung Disease