Growth differentiation factor 15 (GDF15): A survival protein with therapeutic potential in metabolic diseases

Abstract

Growth Differentiation Factor 15 (GDF15), also known as NSAID activated gene-1 (NAG-1), is associated with a large number of biological processes and diseases, including cancer and obesity. GDF15 is synthesized as pro-GDF15, is dimerized, and is cleaved and secreted into the circulation as a mature dimer GDF15. Both the intracellular GDF15 and the circulating mature GDF15 are implicated in biological processes, such as energy homeostasis and body weight regulation. Although there have been many studies on GDF15, GFRAL, a member of the glial-derived neurotropic factor receptor α family, has only been recently identified as a receptor for mature GDF15. In this review, we focused on cancer and energy homeostasis along with obesity and body weight, and the effect of the identification of the GDF15 receptor in these investigations. In addition, the therapeutic potential of GDF15 as a pharmacological agent in obesity and other metabolic diseases was discussed.

Growth Differentiation Factor 15 Ameliorates Anti-Glomerular Basement Membrane Glomerulonephritis in Mice

“…GDF15 is a regulator of inflammatory response dendritic cells maturation [ 16 ] and peripheral blood mononuclear proliferation [ 17 ]. Moreover, its role was suggested in cervical cancer, glioblastoma, cardiovascular ischemic stress, obesity, and metabolic disease, such as mitochondrial myopathies [ 18 , 19 , 20 , 21 , 22 , 23 , 24 ]. However, the knowledge of its role in progression of glomerulonephritis (GN) and mechanisms of function is still limited and requires further investigation.…”

Anti-proliferative activity of A. Oxyphylla and its bioactive constituent nootkatone in colorectal cancer cells

“…The 133 bp promoter region of NAG-1 contains several transcriptional binding sites, including C/EBPβ [36], p53 [37], EGR-1 [19], and Sp1 [12]. These transcription factors are responsible for the downstream effects of several anticancer compounds including COX inhibitors, PPARγ ligands and cancer chemo-preventive agents [38] which increase NAG-1 transcription. Interestingly, sulindac sulfide (or troglitazone)-mediated NAG-1 up-regulation is dependent on the transcription factor EGR-1 in colon cancer cells [39].…”

Growth Differentiation Factor 15 is a potential biomarker of therapeutic response for TK2 deficient myopathy

“…Both GDF-15 and FGF-21 are broad action cytokine/hormone that are altered at the same time in many disease states where they are routinely employed as diagnostic and prognostic biomarkers 12,[20][21][22][23][24][25] . In particular, they are increasingly used individually or in combination as diagnostic biomarkers of mitochondrial diseases 9,16,18 .…”

“…Both GDF-15 and FGF-21 have a role in inflammation, for example, in pancreas, heart and adipose tissue 13,[21][22][23] . Our data show that the profile of inflammatory cytokines was not consistently altered at baseline (not even in the children with the most severe early-onset phenotype) indicating that the elevated levels of GDF-15 and FGF-21 are not secondary to systemic inflammation.…”