Growth Differentiation Factor-15 (GDF-15) belongs to the TGF-β superfamily, synthesized initially as a proprotein. Upon cleavage of the protein, the N-terminal peptide is released to form the mature GDF-15, which is then secreted into the bloodstream as a 25kD dimer. Initially discovered in activated macrophages and with high expression levels in the placenta under normal conditions, it is also known as Macrophage Inhibitory Cytokine-1 (MIC-1) and Placental Transforming Growth Factor-β (PTGF-β). In healthy individuals, GDF-15 is expressed at very low levels in tissues other than the placenta; however, its expression significantly increases in pathological conditions such as inflammation, tumors, and cardiovascular diseases.
GDF-15 is extensively studied in the context of cardiovascular diseases and tumor development. Normally absent in adult cardiac muscle, GDF-15 is significantly expressed by cardiac muscle cells, adipocytes, macrophages, endothelial cells, and vascular smooth muscle cells within the heart following cardiac injury. Consequently, it is referred to by some scholars as a "cardiokine," playing a role similar to adipokines. In tumor development, some studies have observed a marked upregulation of GDF-15 mRNA transcription in tumor biopsy samples. GDF-15 is one of the major secreted proteins induced by the tumor suppressor p53 to inhibit tumor growth. Moreover, the tumor microenvironment can promote tumor angiogenesis by increasing the secretion of GDF-15.
