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

Transforming growth factor-beta (TGFbeta) belongs to a family of multifunctional polypeptides which regulate normal cell growth, development, and tissue remodeling following injury. The ability of cells to produce TGFbeta or to respond to this growth factor via cell surface receptors is highly conserved throughout the animal kingdom. TGFbeta is a potent growth inhibitor of many normal and transformed cell lines; abnormalities in TGFbeta signaling have been linked to tumorigenicity. Disruption of the TGFbeta1 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. TGFbeta 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 TGFbeta genes, dissection of the mechanisms by which TGFbetas are produced and activated, and identification of TGFbeta signaling pathways have established the important roles that these family members play in cell and tissue homeostasis. In this overview, TGFbeta structure-function relationships and their relevance to a few select models of tissue injury/wound repair are highlighted.