GDF15, an update of the physiological and pathological roles it plays: a review
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
Authors: Assadi, Artin; Zahabi, Azadeh; Hart, Robert A.
Abstract
Growth differentiation factor 15 (GDF15) is a peptide hormone, and a divergent member of the transforming growth factor beta (TGF beta) superfamily. In normal physiology, GDF15 is expressed in multiple tissues at a low concentration. GDF15 is overexpressed during and following many pathological conditions such as tissue injury and inflammation in order to play a protective role. However, GDF15 appears to promote tumour growth in the later stages of malignant cancer. The recently identified endogenous receptor for GDF15, GDNF family receptor a-like (GFRAL), has allowed elucidation of a physiological pathway in which GDF15 regulates energy homeostasis and body weight, primarily via appetite suppression. The anorectic effect of GDF15 provides some therapeutic potential in management of cancer-related anorexia/cachexia and obesity. Despite the identification of GFRAL as a GDF15 receptor, there appears to be other signalling mechanisms utilized by GDF15 that further increase the possibility of development of therapeutic treatments, should these pathways be fully characterized. In this review, GDF15 function in both physiological and pathological conditions in various tissues will be discussed.
GDF15 and Growth Control
FRONTIERS IN PHYSIOLOGY
Authors: Emmerson, Paul J.; Duffin, Kevin L.; Chintharlapalli, Sudhakar; Wu, Xinle
Abstract
Growth/differentiation factor-15 (GDF-15) is a distant member of the transforming growth factor beta (TGF-beta) superfamily and is widely expressed in multiple mammalian tissues. Its expression is highly regulated and is often induced in response to conditions associated with cellular stress. GDF15 serum levels have a strong association with many diseases, including inflammation, cancer, cardiovascular diseases, and obesity, and potentially serve as reliable predictor of disease progression. A functional role for GDF15 has been suggested in cancer, cardiovascular disease, kidney disease and metabolic disease. However, the knowledge of its pathophysiological function at the molecular level is still limited and requires more investigation. Recent identification of the endogenous receptor for GDF15 may provide additional insight in to its' molecular mechanisms and relationship to disease states.