Figure 6.

Scleraxis (red text) regulation of gene expression in fibrosis. Extracellular matrix (ECM) synthesis and processing require large quantities of ATP, which may be derived from various intracellular metabolic pathways, including fatty acid b-oxidation, glycolysis, glucose oxidation, and glutaminolysis. Key enzymes of each pathway are depicted, including those of glutaminolysis (green text). Red arrows highlight mechanisms that may contribute to cardiac fibrosis: scleraxis regulates GLS1 expression, per the present results, and shows evidence of regulation of other glutaminolysis enzyme genes. Scleraxis also directly transactivates a variety of pro-fibrotic genes, including ECM components Col1α2 and EDA-Fn; thus, scleraxis may regulate fibrosis by controlling both ECM gene expression and glutaminolysis genes to provide the energy necessary to support fibrosis.