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Wikipedia

GDF15

January 01, 1970

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]

GDF15
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesGDF15, GDF-15, MIC-1, MIC1, NAG-1, PDF, PLAB, PTGFB, growth differentiation factor 15, TGF-PL
External IDsOMIM: 605312 MGI: 1346047 HomoloGene: 3576 GeneCards: GDF15
Orthologs
SpeciesHumanMouse
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 MbChr 8: 71.08 – 71.09 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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 edit

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 edit

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 edit

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000130513 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000038508 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Bootcov MR, Bauskin AR, Valenzuela SM, Moore AG, Bansal M, He XY, et al. (October 1997). "MIC-1, a novel macrophage inhibitory cytokine, is a divergent member of the TGF-beta superfamily". Proceedings of the National Academy of Sciences of the United States of America. 94 (21): 11514–11519. Bibcode:1997PNAS...9411514B. doi:10.1073/pnas.94.21.11514. PMC 23523. PMID 9326641.
  6. ^ a b Zimmers TA, Jin X, Hsiao EC, McGrath SA, Esquela AF, Koniaris LG (June 2005). "Growth differentiation factor-15/macrophage inhibitory cytokine-1 induction after kidney and lung injury". Shock. 23 (6): 543–548. PMID 15897808.
  7. ^ Hsiao EC, Koniaris LG, Zimmers-Koniaris T, Sebald SM, Huynh TV, Lee SJ (May 2000). "Characterization of growth-differentiation factor 15, a transforming growth factor beta superfamily member induced following liver injury". Molecular and Cellular Biology. 20 (10): 3742–3751. doi:10.1128/MCB.20.10.3742-3751.2000. PMC 85678. PMID 10779363.
  8. ^ Ago T, Sadoshima J (February 2006). "GDF15, a cardioprotective TGF-beta superfamily protein". Circulation Research. 98 (3): 294–297. doi:10.1161/01.RES.0000207919.83894.9d. PMID 16484622.
  9. ^ Wollert KC, Kempf T, Lagerqvist B, Lindahl B, Olofsson S, Allhoff T, et al. (October 2007). "Growth differentiation factor 15 for risk stratification and selection of an invasive treatment strategy in non ST-elevation acute coronary syndrome". Circulation. 116 (14): 1540–1548. doi:10.1161/CIRCULATIONAHA.107.697714. PMID 17848615.
  10. ^ Kempf T, Eden M, Strelau J, Naguib M, Willenbockel C, Tongers J, et al. (February 2006). "The transforming growth factor-beta superfamily member growth-differentiation factor-15 protects the heart from ischemia/reperfusion injury". Circulation Research. 98 (3): 351–360. doi:10.1161/01.RES.0000202805.73038.48. PMID 16397141. S2CID 8401462.
  11. ^ Rochette L, Méloux A, Zeller M, Cottin Y, Vergely C (August 2020). "Functional roles of GDF15 in modulating microenvironment to promote carcinogenesis". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1866 (8): 165798. doi:10.1016/j.bbadis.2020.165798. PMID 32304740. S2CID 215819153.
  12. ^ Wallentin L, Zethelius B, Berglund L, Eggers KM, Lind L, Lindahl B, et al. (2013). "GDF-15 for prognostication of cardiovascular and cancer morbidity and mortality in men". PLOS ONE. 8 (12): e78797. Bibcode:2013PLoSO...878797W. doi:10.1371/journal.pone.0078797. PMC 3846468. PMID 24312445.
  13. ^ Wollert KC, Kempf T, Wallentin L (2017-01-01). "Growth Differentiation Factor 15 as a Biomarker in Cardiovascular Disease". Clinical Chemistry. 63 (1): 140–151. doi:10.1373/clinchem.2016.255174. ISSN 0009-9147. PMID 28062617.
  14. ^ Hagström E, James SK, Bertilsson M, Becker RC, Himmelmann A, Husted S, et al. (2016-04-21). "Growth differentiation factor-15 level predicts major bleeding and cardiovascular events in patients with acute coronary syndromes: results from the PLATO study". European Heart Journal. 37 (16): 1325–1333. doi:10.1093/eurheartj/ehv491. ISSN 0195-668X. PMID 26417057.
  15. ^ Luan HH, Wang A, Hilliard BK, Carvalho F, Rosen CE, Ahasic AM, et al. (August 2019). "GDF15 Is an Inflammation-Induced Central Mediator of Tissue Tolerance". Cell. 178 (5): 1231–1244.e11. doi:10.1016/j.cell.2019.07.033. PMC 6863354. PMID 31402172.
  16. ^ Coll AP, Chen M, Taskar P, Rimmington D, Patel S, Tadross JA, et al. (February 2020). "GDF15 mediates the effects of metformin on body weight and energy balance". Nature. 578 (7795): 444–448. doi:10.1038/s41586-019-1911-y. PMC 7234839. PMID 31875646.
  17. ^ Wang D, Townsend LK, DesOrmeaux GJ, Frangos SM, Batchuluun B, Dumont L, et al. (July 2023). "GDF15 promotes weight loss by enhancing energy expenditure in muscle". Nature. 619 (7968): 143–150. Bibcode:2023Natur.619..143W. doi:10.1038/s41586-023-06249-4. PMC 10322716. PMID 37380764.
  18. ^ a b Wang D, Day EA, Townsend LK, Djordjevic D, Jørgensen SB, Steinberg GR (October 2021). "GDF15: emerging biology and therapeutic applications for obesity and cardiometabolic disease". Nature Reviews. Endocrinology. 17 (10): 592–607. doi:10.1038/s41574-021-00529-7. PMID 34381196. S2CID 236972376.
  19. ^ Wang D, Townsend LK, DesOrmeaux GJ, Frangos SM, Batchuluun B, Dumont L, et al. (July 2023). "GDF15 promotes weight loss by enhancing energy expenditure in muscle". Nature. 619 (7968): 143–150. Bibcode:2023Natur.619..143W. doi:10.1038/s41586-023-06249-4. PMC 10322716. PMID 37380764.
  20. ^ Wedel S, Martic I, Guerrero Navarro L, Ploner C, Pierer G, Jansen-Dürr P, et al. (January 2023). "Depletion of growth differentiation factor 15 (GDF15) leads to mitochondrial dysfunction and premature senescence in human dermal fibroblasts". Aging Cell. 22 (1): e13752. doi:10.1111/acel.13752. PMC 9835581. PMID 36547021.
  21. ^ Fejzo M, Rocha N, Cimino I, Lockhart SM, Petry CJ, Kay RG, et al. (2023). "GDF15 linked to maternal risk of nausea and vomiting during pregnancy". Nature. 625 (7996): 760–767. doi:10.1038/s41586-023-06921-9. PMC 10808057. PMID 38092039. S2CID 266233306.

External links edit

  • 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.


 

This article on a gene on human chromosome 19 is a stub. You can help Wikipedia by expanding it.

January 01, 1970
gdf15, growth, differentiation, factor, protein, that, humans, encoded, gene, first, identified, macrophage, inhibitory, cytokine, available, structurespdbortholog, search, pdbe, rcsblist, codes5vt2, 5vz3, 5vz4, 6q2jidentifiersaliases, mic1, plab, ptgfb, growt. 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 GDF15Available structuresPDBOrtholog search PDBe RCSBList of PDB id codes5VT2 5VZ3 5VZ4 6Q2JIdentifiersAliasesGDF15 GDF 15 MIC 1 MIC1 NAG 1 PDF PLAB PTGFB growth differentiation factor 15 TGF PLExternal IDsOMIM 605312 MGI 1346047 HomoloGene 3576 GeneCards GDF15Gene location Human Chr Chromosome 19 human 1 Band19p13 11Start18 374 731 bp 1 End18 389 176 bp 1 Gene location Mouse Chr Chromosome 8 mouse 2 Band8 8 B3 3Start71 082 043 bp 2 End71 085 106 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed inplacentamucosa of urinary bladderkidneybody of pancreasrenal medullastromal cell of endometriumrectumprostateupper lobe of left lungbody of stomachTop expressed incalvarialeft lobe of liverproximal tubulekidneylacrimal glandyolk sacsubmandibular glandjejunumright lung lobeadrenal glandMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functiontransforming growth factor beta receptor binding growth factor activity protein binding cytokine activity protein homodimerization activityCellular componentextracellular region extracellular exosome nucleus cytoplasm extracellular space Golgi apparatus collagen containing extracellular matrixBiological processregulation 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 pathwaySources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez951823886EnsemblENSG00000130513ENSMUSG00000038508UniProtQ99988Q9Z0J7RefSeq mRNA NM 004864NM 011819NM 001330687RefSeq protein NP 004855NP 001317616NP 035949Location UCSC Chr 19 18 37 18 39 MbChr 8 71 08 71 09 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse 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 Contents 1 Function 2 Clinical significance 3 References 4 External linksFunction editThe 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 editGDF15 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 a 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 edit a b c GRCh38 Ensembl release 89 ENSG00000130513 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000038508 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Bootcov MR Bauskin AR Valenzuela SM Moore AG Bansal M He XY et al October 1997 MIC 1 a novel macrophage inhibitory cytokine is a divergent member of the TGF beta superfamily Proceedings of the National Academy of Sciences of the United States of America 94 21 11514 11519 Bibcode 1997PNAS 9411514B doi 10 1073 pnas 94 21 11514 PMC 23523 PMID 9326641 a b Zimmers TA Jin X Hsiao EC McGrath SA Esquela AF Koniaris LG June 2005 Growth differentiation factor 15 macrophage inhibitory cytokine 1 induction after kidney and lung injury Shock 23 6 543 548 PMID 15897808 Hsiao EC Koniaris LG Zimmers Koniaris T Sebald SM Huynh TV Lee SJ May 2000 Characterization of growth differentiation factor 15 a transforming growth factor beta superfamily member induced following liver injury Molecular and Cellular Biology 20 10 3742 3751 doi 10 1128 MCB 20 10 3742 3751 2000 PMC 85678 PMID 10779363 Ago T Sadoshima J February 2006 GDF15 a cardioprotective TGF beta superfamily protein Circulation Research 98 3 294 297 doi 10 1161 01 RES 0000207919 83894 9d PMID 16484622 Wollert KC Kempf T Lagerqvist B Lindahl B Olofsson S Allhoff T et al October 2007 Growth differentiation factor 15 for risk stratification and selection of an invasive treatment strategy in non ST elevation acute coronary syndrome Circulation 116 14 1540 1548 doi 10 1161 CIRCULATIONAHA 107 697714 PMID 17848615 Kempf T Eden M Strelau J Naguib M Willenbockel C Tongers J et al February 2006 The transforming growth factor beta superfamily member growth differentiation factor 15 protects the heart from ischemia reperfusion injury Circulation Research 98 3 351 360 doi 10 1161 01 RES 0000202805 73038 48 PMID 16397141 S2CID 8401462 Rochette L Meloux A Zeller M Cottin Y Vergely C August 2020 Functional roles of GDF15 in modulating microenvironment to promote carcinogenesis Biochimica et Biophysica Acta BBA Molecular Basis of Disease 1866 8 165798 doi 10 1016 j bbadis 2020 165798 PMID 32304740 S2CID 215819153 Wallentin L Zethelius B Berglund L Eggers KM Lind L Lindahl B et al 2013 GDF 15 for prognostication of cardiovascular and cancer morbidity and mortality in men PLOS ONE 8 12 e78797 Bibcode 2013PLoSO 878797W doi 10 1371 journal pone 0078797 PMC 3846468 PMID 24312445 Wollert KC Kempf T Wallentin L 2017 01 01 Growth Differentiation Factor 15 as a Biomarker in Cardiovascular Disease Clinical Chemistry 63 1 140 151 doi 10 1373 clinchem 2016 255174 ISSN 0009 9147 PMID 28062617 Hagstrom E James SK Bertilsson M Becker RC Himmelmann A Husted S et al 2016 04 21 Growth differentiation factor 15 level predicts major bleeding and cardiovascular events in patients with acute coronary syndromes results from the PLATO study European Heart Journal 37 16 1325 1333 doi 10 1093 eurheartj ehv491 ISSN 0195 668X PMID 26417057 Luan HH Wang A Hilliard BK Carvalho F Rosen CE Ahasic AM et al August 2019 GDF15 Is an Inflammation Induced Central Mediator of Tissue Tolerance Cell 178 5 1231 1244 e11 doi 10 1016 j cell 2019 07 033 PMC 6863354 PMID 31402172 Coll AP Chen M Taskar P Rimmington D Patel S Tadross JA et al February 2020 GDF15 mediates the effects of metformin on body weight and energy balance Nature 578 7795 444 448 doi 10 1038 s41586 019 1911 y PMC 7234839 PMID 31875646 Wang D Townsend LK DesOrmeaux GJ Frangos SM Batchuluun B Dumont L et al July 2023 GDF15 promotes weight loss by enhancing energy expenditure in muscle Nature 619 7968 143 150 Bibcode 2023Natur 619 143W doi 10 1038 s41586 023 06249 4 PMC 10322716 PMID 37380764 a b Wang D Day EA Townsend LK Djordjevic D Jorgensen SB Steinberg GR October 2021 GDF15 emerging biology and therapeutic applications for obesity and cardiometabolic disease Nature Reviews Endocrinology 17 10 592 607 doi 10 1038 s41574 021 00529 7 PMID 34381196 S2CID 236972376 Wang D Townsend LK DesOrmeaux GJ Frangos SM Batchuluun B Dumont L et al July 2023 GDF15 promotes weight loss by enhancing energy expenditure in muscle Nature 619 7968 143 150 Bibcode 2023Natur 619 143W doi 10 1038 s41586 023 06249 4 PMC 10322716 PMID 37380764 Wedel S Martic I Guerrero Navarro L Ploner C Pierer G Jansen Durr P et al January 2023 Depletion of growth differentiation factor 15 GDF15 leads to mitochondrial dysfunction and premature senescence in human dermal fibroblasts Aging Cell 22 1 e13752 doi 10 1111 acel 13752 PMC 9835581 PMID 36547021 Fejzo M Rocha N Cimino I Lockhart SM Petry CJ Kay RG et al 2023 GDF15 linked to maternal risk of nausea and vomiting during pregnancy Nature 625 7996 760 767 doi 10 1038 s41586 023 06921 9 PMC 10808057 PMID 38092039 S2CID 266233306 External links editGDF 15 in Oncology Overview of all the structural information available in the PDB for UniProt Q99988 Growth differentiation factor 15 at the PDBe KB nbsp This article on a gene on human chromosome 19 is a stub You can help Wikipedia by expanding it vte Retrieved from https en wikipedia org w index php title GDF15 amp oldid 1216468833, wikipedia, wiki, book, books, library,

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