GDF15

GDF15
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 5VT2, 5VZ3, 5VZ4, 6Q2J
Identifiers
Aliases	GDF15, GDF-15, MIC-1, MIC1, NAG-1, PDF, PLAB, PTGFB, growth differentiation factor 15, TGF-PL
External IDs	OMIM: 605312; MGI: 1346047; HomoloGene: 3576; GeneCards: GDF15; OMA:GDF15 - orthologs
Gene location (Human) Chr. Chromosome 19 (human)[1] Band 19p13.11 Start 18,374,731 bp[1] End 18,389,176 bp[1]
Gene location (Mouse) Chr. Chromosome 8 (mouse)[2] Band 8|8 B3.3 Start 71,082,043 bp[2] End 71,085,106 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in placenta beta cell mucosa of urinary bladder human kidney body of pancreas renal medulla olfactory zone of nasal mucosa decidua stromal cell of endometrium rectum Top expressed in stroma of bone marrow endothelial cell of lymphatic vessel calvaria left lobe of liver right kidney embryo proximal tubule embryo human kidney lacrimal gland More reference expression data BioGPS More reference expression data
Gene ontology Molecular function transforming growth factor beta receptor binding growth factor activity protein binding cytokine activity protein homodimerization activity Cellular component extracellular region extracellular exosome nucleus cytoplasm extracellular space Golgi apparatus collagen-containing extracellular matrix Biological process regulation of apoptotic process cell-cell signaling positive regulation of pathway-restricted SMAD protein phosphorylation positive regulation of myoblast fusion regulation of MAPK cascade transforming growth factor beta receptor signaling pathway cell development signal transduction BMP signaling pathway SMAD protein signal transduction regulation of signaling receptor activity reduction of food intake in response to dietary excess glial cell-derived neurotrophic factor receptor signaling pathway negative regulation of multicellular organism growth positive regulation of MAPK cascade positive regulation of protein kinase B signaling negative regulation of growth hormone receptor signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 9518 23886 Ensembl ENSG00000130513 ENSMUSG00000038508 UniProt Q99988 Q9Z0J7 RefSeq (mRNA) NM_004864 NM_011819 NM_001330687 RefSeq (protein) NP_004855 NP_001317616 NP_035949 Location (UCSC) Chr 19: 18.37 – 18.39 Mb Chr 8: 71.08 – 71.09 Mb PubMed search [3] [4]
Wikidata
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Growth/differentiation factor 15 is a protein that in humans is encoded by the GDF15 gene. GDF15 was first identified as Macrophage inhibitory cytokine-1 or MIC-1.^[5]

It is a protein belonging to the transforming growth factor beta superfamily. Under normal conditions, GDF15 is expressed in low concentrations in most organs and upregulated because of injury of organs such as liver, kidney, heart and lung.^[6][7][8]

Function

The function of GDF15 is not fully clear but it seems to have a role in regulating inflammatory pathways and to be involved in regulating apoptosis, angiogenesis, cell repair and cell growth, which are biological processes observed in cardiovascular and neoplastic disorders.^{[6][9][10][11]}

Clinical significance

GDF15 has shown to be a strong prognostic protein in patients with different diseases such as heart diseases and cancer.^[12] In cardiovascular tissues it is shown that GDF-15 concentrations increase in response to atherosclerosis, ischemia/reperfusion-injury and heart failure.^[13] In patients with coronary artery disease (CAD), GDF-15 is showed to be associated with adverse outcome such as mortality, myocardial infarction, stroke and with bleeding.^[14]

However, elevated GDF15 levels in diseases such as cancer and heart disease may be the result of inflammation caused by these diseases. Note that GDF15 is necessary for surviving both bacterial and viral infections, as well as sepsis. The protective effects of GDF15 were largely independent of pathogen control or the magnitude of inflammatory response, suggesting a role in disease tolerance.^[15]

Metformin was shown to cause increased levels of GDF15. This increase mediates the effect of body weight loss by metformin.^[16] Further study has shown weight loss is promoted by maintaining energy expenditure in addition to appetite suppression.^[17]

Elevations in GDF15 reduce food intake and body mass in animal models through binding to glial cell-derived neurotrophic factor family receptor alpha-like (GFRAL) and the recruitment of the receptor tyrosine kinase RET in the hindbrain.^[18]

In both mice and humans have shown that metformin and exercise increase circulating levels of GDF15. GDF15 might also exert anti-inflammatory effects through mechanisms that are not fully understood. These unique and distinct mechanisms for suppressing food intake and inflammation makes GDF15 an appealing candidate to treat many metabolic diseases, including obesity, type 2 diabetes mellitus, non-alcoholic fatty liver disease, cardiovascular disease and cancer cachexia.^[18]

Treatment of rodents fed a high-fat diet with recombinant growth differentiating factor 15 (GDF15) reduces obesity and improves glycemic control through glial-cell-derived neurotrophic factor family receptor α-like (GFRAL)-dependent suppression of food intake.^[19]

Fibroblast-specific loss of GDF15 expression in a model of 3D reconstructed human skin induced epidermal thinning, a hallmark of skin aging. GDF15 plays a so far undisclosed role in mitochondrial homeostasis to delay both the onset of cellular senescence and the appearance of age-related changes in a 3D human skin model.^[20]

It has been also associated as a causal factor in hyperemesis gravidarum, a severe form of morning sickness.^[21]

References

External links

• GDF 15 in Oncology
• Overview of all the structural information available in the PDB for UniProt: Q99988 (Growth/differentiation factor 15) at the PDBe-KB.

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