Maid is a negative regulator of transforming growth factor-β-induced cell migration

Maternal Id-like molecule (Maid) is a dominant negative helix-loop-helix protein that has been implicated in regulating gene expression as well as cell-cycle progression. Overexpressed Maid was previously shown to inhibit certain cellular responses induced by transforming growth factor-β (TGF-β), such as TGF-β-induced cytostasis and cell motility, but not epithelial-mesenchymal transition (EMT). The role of endogenous Maid in regulating TGF-β signalling, however, has not been elucidated. We have found evidence that endogenous Maid negatively regulates TGF-β-induced cell motility. Maid knockdown enhanced TGF-β-induced cell motility as measured by chamber migration and wound healing assays but did not affect cell motility induced by bone morphogenetic protein (BMP)-4. Endogenous Maid does not appear to be involved in regulating TGF-β-induced cytostasis, resistance to apoptosis or EMT. Notably, Maid expression was induced in the delayed phase (later than 24 h) after TGF-β stimulation whereas the expression of two other negative feedback regulators, Smad7 and SnoN, was induced as early as 1 h after stimulation. These findings indicate that Maid is a unique negative feedback regulator of TGF-β signalling in its mode of action as well as the timing of its induction.