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176 The Role of Fgf10 for Alveogenesis in Bronchopulmonary Dysplasia
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  1. CM Chao1,
  2. D Al Alam2,
  3. C Tiozzo3,
  4. R Virender4,5,
  5. S Bellusci
  1. 1Department of Pediatrics, Excellence Cluster in Cardio-Pulmonary Systems (ECCPS), University of Gießen, Giessen, Germany
  2. 2Developmental Biology and Regenerative Medicine Program, Saban Research Institute of Children’s Hospital
  3. 3Developmental Biology Program, Division of Surgery, Saban Research Institute of Children’s Hospital, Los Angeles
  4. 4Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA
  5. 5Department of Internal Medicine II, Excellence Cluster in Cardio-Pulmonary Systems (ECCPS), University of Gießen, Giessen, Germany

Abstract

Background and aim Bronchopulmonary dysplasia (BPD) is associated with impaired alveolar growth and pathologic vascularization. As a chronic lung disease it remains an important complication for preterm infants, especially born before 28th week of gestational age. Fibroblast-growth-factor 10 (Fgf10) is known to play an important role in lung morphogenesis. We aim to investigate the role of Fgf10 for alveogenesis in a mouse model of BPD.

Methods Using an inducible double transgenic mouse line (SPC-rtTA; tet(O)Fgf10) we established a BPD model by exposing the pups to 85% oxygen (experimental and control group) and normoxia (control group) for 28 days. Activation of the transgene Fgf10 was done after birth (P0) by doxycycline treatment. Gene expressions for Fgfr2b and Fgf10 were analyzed by quantitative real-time PCR. To study lung morphology histology, mean linear intercept (MLI) and radial alveolar count (RAC) were performed.

Results Real-time PCR results showed a significant decrease of Fgfr2b and Fgf10 expression in the hyperoxia group at day 21 and day 28 indicating epithelial cell damages. The histology showed a simplification of alveoli in the hyperoxia group (85% oxygen) but not in the normoxia group after 14 days. In contrast, the hyperoxia group with overexpression of Fgf10 showed less simplification of alveoli. These findings were confirmed by MLI and RAC.

Conclusion We conclude that Fgf10 may have a protective/regenerative effect on lung injury by increasing secondary septa formation.

https://doi.org/10.1136/archdischild-2012-302724.0176

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