MicroRNA regulation of PPARG Signalling: Therapeutic implications for pulmonary hypertension

Gene Ontology (GO) is a tool which provides functional gene annotations and is 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, their contribution to human pathophysiology requires further exploration. Previous studies have identified PPARG participating in multiple signalling pathways, particularly those networks involving TGFB1 and BMP2 in pulmonary arterial smooth muscle cells (PASMCs) and their role in pulmonary arterial hypertension (PAH) pathobiology. To enhance the description of PPARG in the GO resource, we systematically curated the proteins it interacts with and its physiological role in human cells and tissues. In addition, we curated the microRNAs that may play a role in PAH through their regulation of PPARG expression and downstream impact on cellular processes. We curated using robust experimental criteria 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 enhanced the breadth and depth of the GO description of PPARG-associated signalling pathways relevant to the pulmonary vasculature.