In the current study, the involvement of phospholipase D (PLD) in the regulation of collagen type I production was examined using human dermal fibroblasts. Procollagen I production in the cells overexpressing PLD1, but not PLD2 was found to be increased compared with those in the vector control cells. To investigate the role of PLD1, we examined the effect of knockdown of endogenous PLD1 by small interference RNA (siRNA) on collagen production. The reduction of expression levels of PLD1 by siRNA transfection was accompanied by diminution of procollagen biosynthesis and also ribosomal S6 kinase 1 (S6K1) phosphorylation. The activity of mammalian target of rapamycin (mTOR) is essential for phosphorylation of S6K1 and the treatment of dermal fibroblasts with rapamycin, a potent inhibitor of mTOR abolished procollagen I production. These results suggest that PLD1 plays a crucial role in collagen type I production through mTOR signaling in human dermal fibroblast. (c) 2006 Elsevier Inc. All rights reserved.