Rac, PAK and p38 regulate cell contact-dependent nuclear translocation of myocardin-related transcription factor

We investigated the mechanism whereby cell contact injury stimulates the α-smooth muscle actin (SMA) promoter, a key process for epithelial–mesenchymal transition (EMT) during organ fibrosis. Contact disruption by low-Ca2+ medium (LCM) activated Rac, PAK and p38 MAPK, and triggered the nuclear accumulation of myocardin-related transcription factor (MRTF), an inducer of the SMA promoter. Dominant negative (DN) Rac, DN-PAK, DN-p38, or the p38 inhibitor SB203580 suppressed the LCM-induced nuclear accumulation of MRTF and the activation of the SMA promoter. These studies define novel pathway(s) involving Rac, PAK, and p38 in the regulation of MRTF and the contact-dependent induction of EMT.