GDF15 - Growth Differentiation Factor 15 | Elisa - Clia - Antibody - Protein

Background:

GDF-15, a stress-responsive cytokine, stands as a distinct member within the diverse TGF-β superfamily. Its expression is typically low in most tissues during normal physiological conditions. However, when cardiac myocytes face ischemia or heightened ventricular wall stress, GDF-15 expression intensifies significantly. This cytokine has emerged as a potent prognostic indicator in various diseases, including heart diseases and cancer. Interestingly, it appears to act protectively against cardiac injury, attributed to its antihypertrophic, antiapoptotic, and anti-inflammatory properties, although the specific receptor through which GDF-15 exerts its effects remains unidentified. Studies have revealed a positive correlation between elevated GDF-15 levels and factors such as LV mass, IL-6, and MMP-9 levels in patients with heart failure (HF). Notably, GDF-15 has been identified as a reliable predictor of cardiovascular complications in both HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF) patients. Serum GDF-15 levels in HFrEF patients mirror those in HFpEF patients, and they are associated with the severity of HF symptoms as well as echocardiographic parameters indicating LV dysfunction.

Protein Structure:

GDF15 is synthesized as a 308-amino acid prepropeptide. After cleavage of the signal peptide and further proteolytic processing, the mature form is a 25-kDa dimeric protein composed of two identical subunits linked by disulfide bonds. The mature GDF15 protein contains a cysteine knot motif characteristic of the TGF-β superfamily.

Classification and Subtypes:

GDF15 belongs to the TGF-β superfamily, which includes a wide range of growth and differentiation factors involved in various cellular processes such as proliferation, differentiation, and apoptosis. Unlike many members of the TGF-β family that have well-defined developmental roles, GDF15 is more prominently associated with stress responses and disease conditions.

Function and Biological Significance:

• Cellular Stress Response: GDF15 expression is upregulated in response to cellular stress, injury, and inflammation. It acts as a paracrine and endocrine factor to modulate tissue responses to damage.
• Metabolic Regulation: Recent studies have highlighted GDF15's role in metabolic regulation, including appetite suppression and weight loss. It has been implicated in the regulation of energy balance and insulin sensitivity.
• Anti-inflammatory and Anti-apoptotic Effects: GDF15 exhibits protective effects in tissues by reducing inflammation and preventing cell death. This is particularly relevant in conditions such as cardiovascular diseases and tissue injury.

Interactions:

• GFRAL: The GDNF family receptor alpha-like (GFRAL) has been identified as the receptor for GDF15. GFRAL, in complex with the coreceptor RET, mediates the effects of GDF15 on energy homeostasis and appetite regulation.
• Immune Cells: GDF15 interacts with immune cells, modulating their activity during inflammatory responses. It has been shown to inhibit the production of pro-inflammatory cytokines in macrophages and other immune cells.

Clinical Issues:

• Cancer: Elevated levels of GDF15 have been observed in various cancers, including prostate, colorectal, and pancreatic cancers. It is thought to play a role in cancer progression by promoting tumor cell survival, invasion, and resistance to chemotherapy.
• Cardiovascular Diseases: GDF15 serves as a biomarker for cardiovascular diseases. Higher circulating levels of GDF15 are associated with adverse outcomes in heart failure, myocardial infarction, and other cardiac conditions.
• Metabolic Disorders: Increased GDF15 levels are found in metabolic disorders such as obesity and type 2 diabetes. It is being investigated for its potential therapeutic role in managing these conditions due to its effects on weight and glucose metabolism.

Summary:

GDF15 is a stress-induced cytokine belonging to the TGF-β superfamily, playing crucial roles in regulating cellular stress responses, metabolism, and inflammation. It interacts with the GFRAL-RET receptor complex to influence energy balance and appetite. Clinically, GDF15 is a significant biomarker for various diseases, including cancer and cardiovascular disorders, and holds promise for therapeutic interventions in metabolic diseases. Its multifunctional roles and regulatory mechanisms continue to be an active area of research, highlighting its importance in health and disease.