Faady Yahya - Justus-Liebig-Universität Gießen, GER - Pulmonology

Title: CONSTITUTIVE FGF10 DEFICIENCY LEADS TO IMPAIRED EMBRYONIC LUNG DEVELOPMENT

Co-Author(s): Faady Yahya, Cho-Ming Chao

INTRODUCTION: Fgf10 is known to be essential for lung development and regeneration. Our previous data showed that reduced Fgf10 expression leads to delayed embryonic lung development. The aim of this project is to investigate the role of constitutive Fgf10 deficiency in normoxic and

hyperoxic condition (BPD mouse model).

METHODS: 1)Transgenic mouse line of constitutive Fgf10 deficiency (Fgf10+/-, Fgf10 LacZ/-): In WT vs Fgf10+/- and WT vs Fgf10 LacZ/- gene expression analyses (whole lung) at E12.5, E18.5 and PN70 were done by using qRT – PCR (real-time PCR). 2)BPD mouse model: WT vs Fgf10+/- mice were exposed to 85% O2 (hyperoxia) from PN0-PN3. Lungs were harvested at PN3 and gene expression analyses (whole lung) were performed by using real- time PCR. Results were compared to control group under normoxic conditions. 3)Gene expression analyses from 1) and 2) were confirmed on protein level by immunofluorescence (IF) staining (SPC, PECAM, ECAD, KI67) and Western Blot (SPC).

RESULTS: 1) Fgf10 expression is decreased in Fgf10+/- (by 50%) mouse lungs. 2) Constitutive Fgf10 deficiency causes significant changes in gene expression at E18.5 (Fgf10+/- and Fgf10 LacZ/- vs WT): Decreased epithelial marker, increased Tgf-ß signaling and increased of inflammation

markers. Under hyperoxic conditions (hyperoxia PN0-PN3) gene expression is significantly increased for collagen markers, cell cycle genes and Tgf-ß signaling in Fgf10+/- vs WT. 3) In Fgf10+/- mouse lungs at PN3 the IF for Surfactant Protein C (SPC) leads to a considerable decrease of SPC positive cells after hyperoxic injury compared to WT. Western Blot reveals drastic decrease of mature SPC after hyperoxia in Fgf10+/- vs WT.

CONCLUSION: Constitutive Fgf10 deficiency causes changes in gene expression and on protein level relevant for lung development.

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