Figure 2 Signal transduction pathways of transforming growth factor β (TGFβ) and its intracellular mediators, Smad proteins. Active TGFβ released from the latent TGFβ‐binding proteins (LTBP) and latency‐associated peptide (LAP) binds to the specific receptors on the cell surface. Receptor‐activated Smad (R‐Smad) and Smad4 transduce the signal from the cytoplasm to the nucleus, where they regulate target gene transcription usually in association with DNA‐binding transcription factors (TF) and coactivators (Co). By contrast, inhibitory Smad7 is strongly and rapidly induced by TGFβ itself, and acts in an autoregulatory negative feedback loop of the TGFβ/Smad signal. ECM, extracellular matrix.