Functional Genomics Validation of PPAR gamma Signalling in PASMCs: Therapeutic Implications for Pulmonary Arterial Hypertension

Gene Ontology (GO) is a tool which provides gene functional annotations, an essential resource for knowledge discovery and the analysis of biological datasets. Although considerable research has quantified the functional similarity between gene products and physiological processes, there is a need to identify which of these may contribute to pathophysiological states in humans. Previous studies have identified the role of PPARG in multiple signalling pathways, particularly those of TGFB1 and BMP2, in pulmonary artery smooth muscle cells and their relation to pulmonary arterial hypertension (PAH). To enhance the description of PPARG in the GO resource we systematically curated the proteins it interacts with and its physiological role in PASMCs. In addition, we curated the microRNAs that play a role in PAH through their regulation of PPARG expression and their downstream impact on cellular processes. This project curated experimental evidence describing 101 human miRNAs that regulate the expression of 17 PPARG signalling pathway-relevant proteins. Of these, 91 of our curated miRNAs were previously unannotated in terms of directly regulating the expression of these priority proteins. By submitting these annotations to the GO Consortium database, we have significantly expanded the breadth and depth of the GO description of PPARG-associated signalling pathways.