TGF-β-induced SMAD signaling and gene regulation:: consequences for extracellular matrix remodeling and wound healing

Members of the transforming growth factor-beta (TGF-beta) superfamily are pleiotropic cytokines that have the ability to regulate numerous cell functions, including proliferation, differentiation, apoptosis, epithelial-mesenchymal transition, and production of extracellular matrix, allowing them to play an important role during embryonic development and for maintenance of tissue homeostasis. Three TGF-beta isoforms have been identified in mammals. They propagate their signal via a signal transduction network involving receptor serine/threonine kinases at the cell surface and their substrates, the SMAD proteins. Upon phosphorylation and oligomerization, the tatter move into the nucleus to regulate transcription of target genes. This review will summarize recent advances in the understanding of the mechanisms underlying SMAD modulation of extracellular matrix gene expression in the context of wound heating and tissue fibrosis. (C) 2004 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.