EDN1 and gingival overgrowth: However, numerous studies conducted over three decades have suggested that chronic inappropriate increases in levels of local and circulating chemical mediators such as angiotensin II (Ang II) and endothelin-1 (ET-1) and fibrogenic cytokines/proteins such as transforming growth factor (TGF), connective tissue growth factor (CTGF), insulin-like growth factor (IGF), platelet-derived growth factor (PDGF), and mast cell chymase and tryptase enzymes are likely to be key driving forces culminating in gingival overgrowth (Figure 1).