The TGF-βs are members of an essential, multifunctional family of cytokines. These molecules have pivotal roles to play in cell growth and development (at both embryonic and adult stages), during inammation and the maintenance of host resistance mechanisms and within remodelling and repair processes such as angiogenesis and regeneration. Of the three mammalian isoforms of TGF-β (TGF-β1, TGF-β2 and TGF-β3), TGF-β1 is the only member where the homozygous negative mouse can survive following the neonatal period. TGF-β2 and 3 knockout mice die rapidly postnatally [1, 2]. The phenotype of TGF-β±/±mice initially appears quite normal; however, within a couple of weeks after birth the animals develop a severe wasting disease and die within a month [3, 4]. The cause of death has been shown to be massive inammatory lesions in multiple organs, which results in lethal cardiopulmonary failure [5].

TGF-β1, TGF-β2 and TGF-β3 all arise from precursor proteins, which are processed to produce a latent TGF-β complex that is secreted by the cell [6±8]. Either before or after secretion, it can associate with other proteins to form higher molecular weight complexes [9, 10]. The TGF-β receptors, of which at least six have been described [11], either mediate an intracellular signal and/or present TGF-βs to signalling receptors [12]. For TGF-β to be able to signal through these receptors the latent complex must® rst be activated. This process of activation is still not well understood; however, proteins such as plasmin, cathepsin and thrombospondin-1 have all been shown to activate latent TGF-β1 complexes [13±15]. The signal pathways activated by TGF-β are transduced by a series of SMAD proteins [11, 16]. This pathway is very unusual in that there is only one ampli® cation step between the signal being received and the target gene being activated in the nucleus [17].