Presentation description

The transcription factor PPAR gamma (PPARγ) plays an essential role in human lung development. PPARγ regulates genes that take part in the processes that are vital in the lung maturation process, e.g. furthering alveolar development, processes involving epithelial and mesenchymal interactions in the lung, as well as ensuring the vascular integrity of lung tissue. Transcription factors are often subject to alternative splicing, this alternative splicing of transcription factors is generally thought to regulate transactivation of transcription factors. Often times this alternative splicing results in a dominant negative isoform of the transcription factor, lacking transactivation activity. Alternative splicing of PPARγ produces a dominant negative isoform named PPARγ Delta-5 (PPARγΔ5).

Postnatal Growth Restriction (PGR) has been found to play a major role in impaired lung function and development, e.g. reduced alveolar formation and increased distal airways. We demonstrated, for the first time, that PPARγΔ5 is expressed in the developing lung and is increased by PGR in developing rat lungs. However, there are many gaps in understanding of how PGR affects lung development. Including the mechanism of how PGR affects PPARγ's ability to express target genes in lung development, as well as how PGR may be related to the alternative splicing of PPARγ into its less functional counterpart, PPARγΔ5.