TGF-beta signaling pathway: its role in gastrointestinal pathophysiology and modulation of ulcer healing

Gastrointestinal ulcer healing is a complex process, involving cell migration, proliferation, angiogenesis and extracellular matrix deposition, all ultimately leading to reconstruction of tissue architecture within the ulcer scar. These processes are controlled by growth factors, cytokines and hormones. Transforming growth factor-beta (TGF-beta), one of the multifunctional peptide growth factors, has been reported to positively regulate gastrointestinal ulcer healing. Although TGF-beta inhibits cell proliferation in a variety of cells, it induces cell migration, angiogenesis, and enhances extracellular matrix production necessary for gastrointestinal ulcer healing. TGF-beta exerts its action by binding to its transmembrane serine/threonine kinase receptors, which in turn triggers activation of various intracellular signaling pathways. Smads are intermediate effector proteins that play key roles in biological activities of TGF-beta by transmitting the signals from the cell surface directly into the nucleus and initiating transcription. New insight into the mechanisms underlying TGF-beta-Smad modulation of gastrointestinal ulcer healing will likely enhance our understanding of the mechanisms controlling the healing processes of gastrointestinal ulcers.