TGF-β1-induced TAK1 activation triggers downstream signaling pathways such as the MKK4-JNK, or the MKK3-p38 cascade, and promotes degradation of Ik-B, which in turn lead to the activation of transcription factors ATF-2, AP-1 and NF-kB, respectively, to regulate the expression of extracellular matrix proteins, including collagens and fibronectin, and inflammatory cytokines. In addition, TGF-β1-induced Smad activation is also indispensible for TGF-β1-induced type I collagen expression through the crosstalk with TAK1-MKK3-p38 signaling axis.