Growth/differentiation Factor 15 (GDF-15, also called as MIC-1, NAG-1 and NRG-1, Uniprot: Q99988) is a divergent member of the TGF-b superfamily of growth factors. It is encoded in humans by a gene in chromosome 19. The human GDF-15 gene encodes for a protein of 308 amino acid residues which consists of a signal sequence (residues 1-29), pro-domain (30-194) and mature growth factor domain (195-308). The protein is secreted from the producing cell and the precursor containing the pro- and mature domains is proteolytically processed by furin-like protease, typically in the Golgi complex, but sometimes also an unprocessed protein is secreted. Two mature domains dimerize forming a typical TGF-b-like structure with four b-strands and an a-helix in each protomer, with an interfacial disulfide stabilizing the mature growth factor. The molecular weight of a mature GDF-15 dimer is 25 kDa.

Mature GDF-15 has its dedicated GFRAL transmembrane receptor which is found only in very restricted area in the hindbrain. GFRAL facilitates GDF-15 signaling through Ret receptor tyrosine kinase, similar to GDNF subfamily of growth factors.

Approximately 25% of humans have a missense polymorphism in GDF-15 gene resulting in mutation of histidine 202 to aspartate (histidine 6 in the mature domain), close to the N-terminus of the mature growth factor. This variant is associated with phenotypes in prostate cancer, hyperemesis gravidarum, (severe morning sickness in pregnancy) and rheumatoid arthritis. The underlying mechanism and significance of these associations is still unclear though.

GDF-15 expression in healthy subjects is abundant in placenta, followed by the prostate and very low levels in the bladder, kidney, colon, stomach, liver, gall bladder, pancreas, and endometrium1-3. GDF-15 is expressed by cardiomyocytes, adipocytes, macrophages, endothelial and vascular smooth muscle cells4. High circulating GDF-15 concentration are in general related to inflammation, myocardial ischemia, and cancer except for in pregnancies. It is often induced under stress to maintain cell and tissue homeostasis5-6.

GDF-15 is proposed as a diagnostic biomarker in colorectal7-8, ovarian9, early-stage lung cancer8,10. It is shown to be an accurate marker for differentiating pancreatic adenocarcinoma and chronic pancreatitis11. It has also shown to be a potential biomarker to aid in the discrimination between prostate cancer and benign hyperplasia12-14, studied as a biomarker for disease prognosis and as an emerging target for cancer immunotherapy15. Neutralizing antibodies against GDF-15 has been studied to revert the weight loss in animal models of cancer-related cachexia15-17.

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Boutari C, Stefanakis K, Simati S, Guatibonza-García V, Valenzuela-Vallejo L, Anastasiou IA, et al. Circulating total and H-specific GDF15 levels are elevated in subjects with MASLD but not in hyperlipidemic but otherwise metabolically healthy subjects with obesity. Cardiovasc Diabetol. 2024;23(174):1-15. doi:10.1186/s12933-024-02264-5.

All Products Cited: GDF-15 (Total) ELISA AL-1014; GDF-15 (H-Specific) ELISA AL-1018; C-Peptide of Insulin ELISA AL-151

Calvert ME, Kalra B, Patel A, Kumar A, Shaw ND. Serum and urine profiles of TGF-β superfamily members in reproductive aged women. Clin Chim Acta. 2022 Jan 1;524:96-100. doi: 10.1016/j.cca.2021.12.002. Epub 2021 Dec 5. PMID: 34875272; PMCID: PMC8740174.

All Products Cited: Inhibin A (pico) ELISA AL-184; Inhibin B ELISA AL-107; Inhibin (Total) ELISA AL-134; AMH (PCOCheck) ELISA AL-196; Activin A ELISA AL-110; Activin B ELISA AL-150; Activin AB ELISA AL-153; Follistatin ELISA AL-117; GDF-9/BMP-15 Complex ELISA AL-181; GDF-15 (Total) ELISA AL-1014; GDF-15 (H-Specific) ELISA AL-1018

Kalra B, Parekh H, Patel AS, Mistry S, Hyvonen M, Kumar A. Development of Novel ELISAs for Total GDF-15 and H-Specific GDF-15. Ansh Labs, Webster, TX; University of Cambridge, Cambridge, United Kingdom. Poster presentation at the Association for Diagnostics and Laboratory Medicine; 2024; Chicago, Illinois.

All Products Cited: GDF-15 (Total) ELISA AL-1014; GDF-15 (H-Specific) ELISA AL-1018

Valenzuela-Vallejo L, Chrysafi P, Bello-Ramos J, Bsata S, Mantzoros CS. Circulating total and intact GDF-15 levels are not altered in response to weight loss induced by liraglutide or lorcaserin treatment in humans with obesity. Metabolism. 2022 Aug;133:155237. doi: 10.1016/j.metabol.2022.155237. Epub 2022 Jun 11. PMID: 35700837.

All Products Cited: GDF-15 (Total) ELISA AL-1014; GDF-15 (H-Specific) ELISA AL-1018

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