Altered lung developmental pathways during the phase of alveogenesis in mice lacking superoxide dismutase 3, extracellular (SOD3)
2014
Background: Previously we detected impaired lung function in gene targeted Sod3 (-/-) mice and associated two functional SOD3 single nucleotide polymorphisms to decreased forced expiratory volume in 1s and maximal expiratory flow at 25% volume in children. Decreased lung SOD3 levels and activity were detected in JF1/Msf mice (poor lung function) compared to C3H/HeJ mice (higher lung function) with the greatest difference during postnatal (P) days 14- P28 ie. alveogenesis phase. In this work we studied the global lung transcript profile in Sod3 (-/-) mice during alveogenesis. Methods: Lung transcript levels were measured by microarray analysis comparing female P14 and P28 Sod3 (-/-) with matched S od3 (+/+) mice (n=4-16). Significantly altered transcripts (≥2-fold decreased or increased) were analyzed for enriched pathways/categories using Database for Annotation, Visualization, and Integrated Discovery (DAVID), Gene Ontogeny (GO) molecular function, GO biological process, GO cell component, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Results: The GO/KEGG categories for decreased transcripts at P14 (n=1793) and P28 (n= 1047) in S od3 (-/-) mouse lung included Wnt signaling, developmental process, respiratory system development, lung development, MTOR, MAPK, and VEGF signaling. Noteworthy transcripts in these categories include Sftpd, Sftpa1, Wnt4, Wnt1 Wisp1 , Chi3l1, Klf15, Fgfbp1, Spry4, Stk3, and Fgfr4 . Discussion: Our preliminary data indicates altered regulation of key lung developmental pathways during the peak alveogenesis phase in mice lacking SOD3 that may have contributed in impaired lung function development in Sod3 (-/-) mice.
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