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

• Published in: Journal of dermatological science Vol. 35; no. 2; pp. 83 - 92
• Main Authors: Schiller, Meinhard, Javelaud, Delphine, Mauviel, Alain
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ireland Ltd 01.08.2004; Elsevier
• Subjects: Animals; Cancer; Collagen gene expression; DNA-Binding Proteins; DNA-Binding Proteins - metabolism; Extracellular Matrix; Extracellular Matrix - physiology; Fibrosis; Gene Expression Regulation; Humans; Jun-N-terminal kinase; Life Sciences; Signal Transduction; Signal Transduction - physiology; Smad Proteins; Trans-Activators; Trans-Activators - metabolism; Transforming Growth Factor beta; Transforming Growth Factor beta - physiology; Transforming growth factor-β; Wound Healing; Wound Healing - physiology; TβRI/II; Wound healing; BMP; JNK; FKBP12; Jun-N-terminal kinase; ECM; CBP; SKI; NF-κB; IFN-γ; TNF-α; Transforming growth factor-β; TGIF; Fibrosis; PAI-1; TGF-β; MH; SARA; SMAD; NEMO; SnoN; Collagen gene expression; Transforming Growth Factor-Β; Collagen Gene Expression; Wound Healing; Jun N-terminal Kinase
• ISSN: 0923-1811; 1873-569X
• DOI: 10.1016/j.jdermsci.2003.12.006

Members of the transforming growth factor-β (TGF-β) 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-β 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 latter 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 healing and tissue fibrosis.