Figure 2.

Mechanism of collagen gene regulation by scleraxis. Scleraxis expression is increased in response to transforming growth factor (TGF)-β via the canonical Smad signaling pathway [73,75]. Collagen synthesis is upregulated by scleraxis and/or by Smads (for example, Smad3), either independently or synergistically via direct interaction with the collagen gene promoter [75]. It is unclear whether other mechanisms may upregulate scleraxis expression independently of TGF-β (dashed line). These mechanisms may act as a regulatory ‘cassette’, governing cardiac infarct scar formation [73], cardiac fibrosis (and potentially fibrosis in other tissues as well) [73,75], tendon formation [72,77], and possibly keloid formation [78] and wound healing [79]. Therapeutic attenuation of scleraxis expression or activity may provide a means to alter one or more of these processes.