p63 is expressed as multiple variants including TA and Delta N forms. Since p63-deficient mice displayed profound defects of stratified epithelia, p63 is an essential transcription factor required for epidermal morphogenesis. However, precise molecular mechanisms behind contribution of p63 to normal skin formation and healing skin wounds remained unclear. In this study, we demonstrated that Delta Np63/BMP-7 signaling pathway modulates wound healing process through the regulation of extracellular matrix protein matrilin-2. Knocking down of Delta Np63 in human keratinocyte HaCaT cells led to a significant reduction of matrilin-2. Intriguingly, BMP-7 which is one of Delta Np63-target gene products, induced matrilin-2 and attenuated inhibitory effect of siRNA against Delta Np63 on matrilin-2. Furthermore, a remarkable cell migration in response to wounding took place in Delta Np63- or matrilin-2-knocked down cells. Taken together, our present findings indicate that Delta Np63/BMP-7 signaling pathway modulates wound healing process through the regulation of matrilin-2. (C) 2008 Elsevier Inc. All rights reserved.