Schematic representation of the regulation and function of TGF-β1 and SMAD2/3 signaling in the PMFs. TGF-β1, Activin A, and BMP2 activate TGF-β receptor, while Gremlin acts as an antagonist to BMP2-mediated TGF-β1 signaling by binding BMP2 directly. Downstream, TGF-β1 and Activin A favor activation of SMAD2/3, resulting in the expression of genes classically associated with PMF activation. In contrast, BMP2-mediated activation favors SMAD1/5/8 activation in PMFs, which competes with SMAD2/3 for SMAD4, thereby abrogating PMF activation signatures