Role of transforming growth factor-β in tissue injury and repair

Transforming growth factor-β (TGFβ) belongs to a family of multifunctional polypeptides which regulate normal cell growth, development, and tissue remodeling following injury. The ability of cells to produce TGFβ or to respond to this growth factor via cell surface receptors is highly conserved throughout the animal kingdom. TGFβ is a potent growth inhibitor of many normal and transformed cell lines; abnormalities in TGFβ signaling have been linked to tumorigenicity. Disruption of the TGFβ1 gene in utero produces a wasting syndrome characterized by systemic inflammation, suggesting that this growth factor plays an important role in limiting the inflammatory response. TGFβ is a dominant mediator of the pathologic extracellular matrix accumulation that characterizes progression of tissue injury to end-stage organ failure. Recent studies directed towards characterization of the TGFβ genes, dissection of the mechanisms by which TGFβs are produced and activated, and identification of TGFβ signaling pathways have established the important roles that these family members play in cell and tissue homeostasis. In this overview, TGFβ structure-function relationships and their relevance to a few select models of tissue injury/wound repair are highlighted.