Transforming growth factor-β in smooth muscle cell differentiation. In the initiation stage of smooth muscle cell (SMC) differentiation, transforming growth factor (TGF)-β rapidly activates Smad signaling, leading to the activation of SMC early marker genes and cell fate determination by interacting with other transcription factors (TFs). At later stages, myocardin or MRTFs, via interacting with SRF, Smads and other TFs, enforce and accelerate SMC differentiation and maturation. In both the initial or later stages, other signaling pathways including PI3K, MAPK, RhoA, Notch, and miRNA may participate in the regulation of the differentiation process by interacting with TGF-β signaling molecules or downstream targets.