The multiple facets of the TGF-β family cytokine growth/differentiation factor-15/macrophage inhibitory cytokine-1

GDF-15 (also MIC-1, NAG-1, PLAB, PTGFB) is a member of the TGF-β superfamily, which is widely distributed in mammalian tissues and has been shown to play multiple roles in various pathologies, including inflammation, cancer, cardiovascular diseases, and obesity. GDF-15 serum levels are a highly reliable predictor of disease progression. Both the anti-tumorigenic potential of GDF-15 and its capacity to promote metastasis have been documented for a large variety of cancers, yet its opposing functions, which are typical for members of the TGF-β superfamily, have only partly been resolved on the molecular level. Knowledge on physiological functions in the non-diseased organism is scarce. In the nervous system GDF-15 knockout analyses have revealed that GDF-15 is essential for the postnatal maintenance of various neuron populations. When applied exogenously GDF-15 is a powerful factor for promoting survival of developing and lesioned neurons in vitro and in vivo. Receptor activation by GDF-15 has only been partially resolved.