Transforming growth factor-beta: a key mediator of fibrosis.
Transforming growth factor (TGF)-beta is a prototypic multifunctional cytokine whose broad modulatory mechanisms affect numerous biological functions both at the cell and organism levels. These include, but are not limited to, control of immune functions, embryogenesis, carcinogenesis, tissue responses to injury, cell proliferation, extracellular matrix (ECM) synthesis and degradation, and cell migration. The identification of Smad proteins, TGF-beta receptor kinase substrates that translocate into the cell nucleus to act as transcription factors, has increased our understanding of the molecular mechanisms underlying TGF-beta action. This introductory chapter will outline the current knowledge on how specific signals initiated by the TGF-beta receptors are brought to the nucleus to regulate gene expression, with a specific emphasis on how such signaling relates to connective tissue remodeling, repair, and fibrosis.
Mauviel
Alain
A
INSERM U697, Hopital Saint-Louis, Paris, France.
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D003094:Collagen / Q000737:chemistry; D005109:Extracellular Matrix / Q000378:metabolism; D005355:Fibrosis / Q000175:diagnosis / Q000209:etiology* / Q000473:pathology*; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation; D008954:Models, Biological; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000502:physiology*
D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D003094:Collagen; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I