Gene Symbol: Gdf15
Description: growth differentiation factor 15
Alias: MIC-1, NAG-1, SBF, growth/differentiation factor 15, macrophage inhibiting cytokine-1
Species: mouse
Products:     Gdf15

Top Publications

  1. Kempf T, Eden M, Strelau J, Naguib M, Willenbockel C, Tongers J, et al. The transforming growth factor-beta superfamily member growth-differentiation factor-15 protects the heart from ischemia/reperfusion injury. Circ Res. 2006;98:351-60 pubmed
    ..In conclusion, our study identifies induction of GDF-15 in the heart as a novel defense mechanism that protects from I/R injury. ..
  2. Cekanova M, Lee S, Donnell R, Sukhthankar M, Eling T, Fischer S, et al. Nonsteroidal anti-inflammatory drug-activated gene-1 expression inhibits urethane-induced pulmonary tumorigenesis in transgenic mice. Cancer Prev Res (Phila). 2009;2:450-8 pubmed publisher
    ..Overall, our study revealed for the first time that the NAG-1 protein inhibits urethane-induced tumor formation, probably mediated by the p38 MAPK pathway, and is a possible new target for lung cancer chemoprevention...
  3. Tsai V, Macia L, Johnen H, Kuffner T, Manadhar R, Jørgensen S, et al. TGF-b superfamily cytokine MIC-1/GDF15 is a physiological appetite and body weight regulator. PLoS ONE. 2013;8:e55174 pubmed publisher
    The TGF-b superfamily cytokine MIC-1/GDF15 circulates in all humans and when overproduced in cancer leads to anorexia/cachexia, by direct action on brain feeding centres...
  4. Bottner M, Laaff M, Schechinger B, Rappold G, Unsicker K, Suter Crazzolara C. Characterization of the rat, mouse, and human genes of growth/differentiation factor-15/macrophage inhibiting cytokine-1 (GDF-15/MIC-1). Gene. 1999;237:105-11 pubmed
    ..Deletion analysis suggests that a 350 bp region upstream of the start of the open reading frame appears to be the most important for regulation of transcription. ..
  5. de Jager S, Bermudez B, Bot I, Koenen R, Bot M, Kavelaars A, et al. Growth differentiation factor 15 deficiency protects against atherosclerosis by attenuating CCR2-mediated macrophage chemotaxis. J Exp Med. 2011;208:217-25 pubmed publisher
    ..Our study is the first to identify GDF-15 as an acute phase modifier of CCR2/TGF?RII-dependent inflammatory responses to vascular injury. ..
  6. Hsiao E, Koniaris L, Zimmers Koniaris T, Sebald S, Huynh T, Lee S. Characterization of growth-differentiation factor 15, a transforming growth factor beta superfamily member induced following liver injury. Mol Cell Biol. 2000;20:3742-51 pubmed
    ..have identified a new murine transforming growth factor beta superfamily member, growth-differentiation factor 15 (Gdf15), that is expressed at highest levels in adult liver...
  7. Husaini Y, Qiu M, Lockwood G, Luo X, Shang P, Kuffner T, et al. Macrophage inhibitory cytokine-1 (MIC-1/GDF15) slows cancer development but increases metastases in TRAMP prostate cancer prone mice. PLoS ONE. 2012;7:e43833 pubmed publisher
    Macrophage inhibitory cytokine-1 (MIC-1/GDF15), a divergent member of the TGF-? superfamily, is over-expressed by many common cancers including those of the prostate (PCa) and its expression is linked to cancer outcome...
  8. Schindowski K, Von Bohlen Und Halbach O, Strelau J, Ridder D, Herrmann O, Schober A, et al. Regulation of GDF-15, a distant TGF-? superfamily member, in a mouse model of cerebral ischemia. Cell Tissue Res. 2011;343:399-409 pubmed publisher
    ..Together, our data substantiate the notion that GDF-15 is prominently upregulated in the lesioned brain and might be involved in orchestrating post-lesional responses other than the trophic support of neurons. ..
  9. Ding Q, Mracek T, Gonzalez Muniesa P, Kos K, Wilding J, Trayhurn P, et al. Identification of macrophage inhibitory cytokine-1 in adipose tissue and its secretion as an adipokine by human adipocytes. Endocrinology. 2009;150:1688-96 pubmed publisher
    ..We conclude that MIC-1 is expressed in adipose tissue and secreted from adipocytes and is therefore a new adipokine. MIC-1 may have a paracrine role in the modulation of adipose tissue function and body fat mass. ..

Scientific Experts

More Information


  1. Noorali S, Kurita T, Woolcock B, de Algara T, Lo M, Paralkar V, et al. Dynamics of expression of growth differentiation factor 15 in normal and PIN development in the mouse. Differentiation. 2007;75:325-36 pubmed
    Growth differentiation factor (GDF15) is a distant member of the transforming growth factor-beta superfamily, a diverse group of structurally related proteins that exert multiple effects on cell fate such as on cell growth and ..
  2. Xu J, Kimball T, Lorenz J, Brown D, Bauskin A, Klevitsky R, et al. GDF15/MIC-1 functions as a protective and antihypertrophic factor released from the myocardium in association with SMAD protein activation. Circ Res. 2006;98:342-50 pubmed
    Here we identified growth-differentiation factor 15 (GDF15) (also known as MIC-1), a secreted member of the transforming growth factor (TGF)-beta superfamily, as a novel antihypertrophic regulatory factor in the heart...
  3. Zimmers T, Jin X, Hsiao E, Perez E, Pierce R, Chavin K, et al. Growth differentiation factor-15: induction in liver injury through p53 and tumor necrosis factor-independent mechanisms. J Surg Res. 2006;130:45-51 pubmed
    ..b>Gdf15 induction was independent of protein synthesis, a hallmark of immediate-early gene regulation...
  4. Zimmers T, Jin X, Gutierrez J, Acosta C, McKillop I, Pierce R, et al. Effect of in vivo loss of GDF-15 on hepatocellular carcinogenesis. J Cancer Res Clin Oncol. 2008;134:753-9 pubmed publisher
    ..The current study sought to determine the effect of GDF-15 ablation on the development of hepatocellular carcinoma (HCC) in vivo...
  5. Strelau J, Strzelczyk A, Rusu P, Bendner G, Wiese S, Diella F, et al. Progressive postnatal motoneuron loss in mice lacking GDF-15. J Neurosci. 2009;29:13640-8 pubmed publisher
  6. Roth P, Junker M, Tritschler I, Mittelbronn M, Dombrowski Y, Breit S, et al. GDF-15 contributes to proliferation and immune escape of malignant gliomas. Clin Cancer Res. 2010;16:3851-9 pubmed publisher
  7. Kempf T, Zarbock A, Widera C, Butz S, Stadtmann A, Rossaint J, et al. GDF-15 is an inhibitor of leukocyte integrin activation required for survival after myocardial infarction in mice. Nat Med. 2011;17:581-8 pubmed publisher
    ..We show that coronary artery ligation in Gdf15-deficient mice led to enhanced recruitment of polymorphonuclear leukocytes (PMNs) into the infarcted myocardium ..
  8. Macia L, Tsai V, Nguyen A, Johnen H, Kuffner T, Shi Y, et al. Macrophage inhibitory cytokine 1 (MIC-1/GDF15) decreases food intake, body weight and improves glucose tolerance in mice on normal & obesogenic diets. PLoS ONE. 2012;7:e34868 pubmed publisher
    ..Here we show that that macrophage inhibitory cytokine-1 (MIC-1/GDF15), known to have anorexigenic effects particularly in cancer, provides protection against the development of ..
  9. Subramaniam S, Strelau J, Unsicker K. Growth differentiation factor-15 prevents low potassium-induced cell death of cerebellar granule neurons by differential regulation of Akt and ERK pathways. J Biol Chem. 2003;278:8904-12 pubmed
    ..Furthermore, we show that GDF-15 prevented generation of reactive oxygen species, a known activator of ERK. Together, our data suggest that GDF-15 prevents apoptosis in CGN by activating Akt and inhibiting endogenously active ERK. ..
  10. Preusch M, Baeuerle M, Albrecht C, Blessing E, Bischof M, Katus H, et al. GDF-15 protects from macrophage accumulation in a mousemodel of advanced atherosclerosis. Eur J Med Res. 2013;18:19 pubmed publisher
    ..This is the first study that demonstrates a protective role of GDF-15 in advanced atherosclerosis and macrophage accumulation, possibly due to the reduced expression of adhesion molecules. ..
  11. Ge Y, Waldemer R, Nalluri R, Nuzzi P, Chen J. RNAi screen reveals potentially novel roles of cytokines in myoblast differentiation. PLoS ONE. 2013;8:e68068 pubmed publisher
  12. Husaini Y, Lockwood G, Nguyen T, Tsai V, Mohammad M, Russell P, et al. Macrophage inhibitory cytokine-1 (MIC-1/GDF15) gene deletion promotes cancer growth in TRAMP prostate cancer prone mice. PLoS ONE. 2015;10:e0115189 pubmed publisher
    The divergent TGF-β superfamily member, macrophage inhibitory cytokine-1 (MIC-1/GDF15), is overexpressed by most cancers, including prostate cancer (PCa)...
  13. Herter J, Kraft F, Van Aken H, Meersch M, Zarbock A, Rossaint J. GDF-15 prevents ventilator-induced lung injury by inhibiting the formation of platelet-neutrophil aggregates. Thromb Haemost. 2015;114:434-7 pubmed publisher
  14. Mazagova M, Buikema H, Landheer S, Vavrinec P, Buiten A, Henning R, et al. Growth differentiation factor 15 impairs aortic contractile and relaxing function through altered caveolar signaling of the endothelium. Am J Physiol Heart Circ Physiol. 2013;304:H709-18 pubmed publisher
    b>Growth differentiation factor 15 (GDF15) is an independent predictor of cardiovascular disease, and increased GDF15 levels have been associated with endothelial dysfunction in selected patients...
  15. Wang X, Krebbers J, Charalambous P, Machado V, Schober A, Bosse F, et al. Growth/differentiation factor-15 and its role in peripheral nervous system lesion and regeneration. Cell Tissue Res. 2015;362:317-30 pubmed publisher
    ..Furthermore, the regenerated WT nerve showed better performance in the electromyography test, indicating better functional recovery. We conclude that endogenous GDF-15 is beneficial for axon regeneration following SN crush. ..
  16. Widera C, Giannitsis E, Kempf T, Korf Klingebiel M, Fiedler B, Sharma S, et al. Identification of follistatin-like 1 by expression cloning as an activator of the growth differentiation factor 15 gene and a prognostic biomarker in acute coronary syndrome. Clin Chem. 2012;58:1233-41 pubmed publisher
    b>Growth differentiation factor 15 (GDF15) is a stress-responsive cytokine and biomarker that is produced after myocardial infarction and that is related to prognosis in acute coronary syndrome (ACS)...
  17. Low J, Ambikairajah A, Shang K, Brown D, Tsai V, Breit S, et al. First Behavioural Characterisation of a Knockout Mouse Model for the Transforming Growth Factor (TGF)-? Superfamily Cytokine, MIC-1/GDF15. PLoS ONE. 2017;12:e0168416 pubmed publisher
    Macrophage inhibitory cytokine-1 (MIC-1), also known as growth differentiation factor 15 (GDF15), is a stress response cytokine...
  18. Liu D, Lu J, Zhao Q, Hu C, Mei Y. Growth differentiation factor-15 promotes glutamate release in medial prefrontal cortex of mice through upregulation of T-type calcium channels. Sci Rep. 2016;6:28653 pubmed publisher
  19. Hsu J, Crawley S, Chen M, Ayupova D, Lindhout D, Higbee J, et al. Non-homeostatic body weight regulation through a brainstem-restricted receptor for GDF15. Nature. 2017;550:255-259 pubmed publisher
    ..GDNF) receptor alpha-like (GFRAL) as a brainstem-restricted receptor for growth and differentiation factor 15 (GDF15)...
  20. Mazagova M, Buikema H, van Buiten A, Duin M, Goris M, Sandovici M, et al. Genetic deletion of growth differentiation factor 15 augments renal damage in both type 1 and type 2 models of diabetes. Am J Physiol Renal Physiol. 2013;305:F1249-64 pubmed publisher
    b>Growth differentiation factor 15 (GDF15) is emerging as valuable biomarker in cardiovascular disease and diabetic kidney disease...
  21. Morrow R, Picard M, Derbeneva O, Leipzig J, McManus M, Gouspillou G, et al. Mitochondrial energy deficiency leads to hyperproliferation of skeletal muscle mitochondria and enhanced insulin sensitivity. Proc Natl Acad Sci U S A. 2017;114:2705-2710 pubmed publisher
    ..down-regulation of diabetes-related genes, and increased expression of the genes encoding the myokines FGF21 and GDF15. However, FGF21 was not elevated in serum, and FGF21 and UCP1 mRNAs were not induced in liver or brown adipose ..
  22. Zhang Y, Jiang W, Wang L, Lingappan K. Sex-specific differences in the modulation of Growth Differentiation Factor 15 (GDF15) by hyperoxia in vivo and in vitro: Role of Hif-1?. Toxicol Appl Pharmacol. 2017;332:8-14 pubmed publisher
    ..The reasons underlying sexually dimorphic outcomes in premature neonates are not known. GDF15 (Growth and differentiation factor 15) is a secreted cytokine and plays a role in cell proliferation, apoptosis, ..
  23. Zimmers T, Jin X, Hsiao E, McGrath S, Esquela A, Koniaris L. Growth differentiation factor-15/macrophage inhibitory cytokine-1 induction after kidney and lung injury. Shock. 2005;23:543-8 pubmed
    ..b>Gdf15 induction was independent of protein synthesis, a hallmark of immediate-early gene regulation...
  24. Rossaint J, Vestweber D, Zarbock A. GDF-15 prevents platelet integrin activation and thrombus formation. J Thromb Haemost. 2013;11:335-44 pubmed publisher
    ..GDF-15 specifically inhibits platelet integrin activation. These findings may have profound clinical implications for the treatment of hemostatic conditions involving platelets. ..
  25. Johnen H, Kuffner T, Brown D, Wu B, Stocker R, Breit S. Increased expression of the TGF-b superfamily cytokine MIC-1/GDF15 protects ApoE(-/-) mice from the development of atherosclerosis. Cardiovasc Pathol. 2012;21:499-505 pubmed publisher
    MIC-1/GDF15 is a member of the TGF-b superfamily, which is thought to have pleiotropic roles in stress responses, inflammation, tissue injury and repair, energy homeostasis, and malignancy...
  26. Chung H, Ryu D, Kim K, Chang J, Kim Y, Yi H, et al. Growth differentiation factor 15 is a myomitokine governing systemic energy homeostasis. J Cell Biol. 2017;216:149-165 pubmed publisher
    ..knockout [MKO]), an integral protein of the large mitoribosomal subunit (39S), we identified growth differentiation factor 15 (GDF15) as a UPRmt-associated cell-non-autonomous myomitokine that regulates systemic ..
  27. Iguchi G, Chrysovergis K, Lee S, Baek S, Langenbach R, Eling T. A reciprocal relationship exists between non-steroidal anti-inflammatory drug-activated gene-1 (NAG-1) and cyclooxygenase-2. Cancer Lett. 2009;282:152-8 pubmed publisher
    ..Furthermore, PGE(2) reduces NAG-1 while celebrex induces NAG-1 expression. The results suggest that a possible inverse relationship exists between the expression of NAG-1 and COX-2 in tumor formation of colon tissue. ..
  28. Lambrecht S, Smith V, De Wilde K, Coudenys J, Decuman S, Deforce D, et al. Growth differentiation factor 15, a marker of lung involvement in systemic sclerosis, is involved in fibrosis development but is not indispensable for fibrosis development. Arthritis Rheumatol. 2014;66:418-27 pubmed publisher
    ..b>Growth differentiation factor 15 (GDF-15) is a distant member of this family...
  29. Zhou Z, Li W, Song Y, Wang L, Zhang K, Yang J, et al. Growth differentiation factor-15 suppresses maturation and function of dendritic cells and inhibits tumor-specific immune response. PLoS ONE. 2013;8:e78618 pubmed publisher
    ..These results indicate that GDF-15 may be one of the critical molecules that inhibit DC maturation and function and are involved in tumor immune escape. Thus, GDF-15 may be a novel target in tumor immunotherapy. ..
  30. Wang X, Chrysovergis K, Kosak J, Kissling G, Streicker M, Moser G, et al. hNAG-1 increases lifespan by regulating energy metabolism and insulin/IGF-1/mTOR signaling. Aging (Albany NY). 2014;6:690-704 pubmed
    Nonsteroidal anti-inflammatory drug-activated gene (NAG-1) or GDF15 is a divergent member of the transforming growth factor beta (TGF-β) superfamily and mice expressing hNAG-1/hGDF15 have been shown to be resistant to HFD-induced ..
  31. Huh S, Chung C, Sharma A, Robertson G. Macrophage inhibitory cytokine-1 regulates melanoma vascular development. Am J Pathol. 2010;176:2948-57 pubmed publisher
    ..Thus, MIC-1 is secreted from melanoma cells together with VEGF to promote vascular development mediated by (V600E)B-Raf signaling. ..
  32. Bonaterra G, Zügel S, Thogersen J, Walter S, Haberkorn U, Strelau J, et al. Growth differentiation factor-15 deficiency inhibits atherosclerosis progression by regulating interleukin-6-dependent inflammatory response to vascular injury. J Am Heart Assoc. 2012;1:e002550 pubmed publisher
    ..Our data suggest that GDF-15 is involved in orchestrating atherosclerotic lesion progression by regulating apoptotic cell death and IL-6-dependent inflammatory responses to vascular injury. ..
  33. Yin T, Cho S, Chen X. RNPC1, an RNA-binding protein and a p53 target, regulates macrophage inhibitory cytokine-1 (MIC-1) expression through mRNA stability. J Biol Chem. 2013;288:23680-6 pubmed publisher
    ..Altogether, we uncover a novel mechanism by which MIC-1 can be regulated through RNPC1 via mRNA stability. ..
  34. Machado V, Haas S, Von Bohlen Und Halbach O, Wree A, Krieglstein K, Unsicker K, et al. Growth/differentiation factor-15 deficiency compromises dopaminergic neuron survival and microglial response in the 6-hydroxydopamine mouse model of Parkinson's disease. Neurobiol Dis. 2016;88:1-15 pubmed publisher
    ..Taken together, these results indicate the importance of Gdf-15 in promoting survival of DAergic neurons and regulating the inflammatory response post 6-OHDA lesion. ..
  35. Hinoi E, Ochi H, Takarada T, Nakatani E, Iezaki T, Nakajima H, et al. Positive regulation of osteoclastic differentiation by growth differentiation factor 15 upregulated in osteocytic cells under hypoxia. J Bone Miner Res. 2012;27:938-49 pubmed publisher
    ..Using microarray and real-time PCR analyses, we identified growth differentiation factor 15 (GDF15) as a key candidate factor secreted from osteocytes under hypoxia...
  36. Artz A, Butz S, Vestweber D. GDF-15 inhibits integrin activation and mouse neutrophil recruitment through the ALK-5/TGF-?RII heterodimer. Blood. 2016;128:529-41 pubmed publisher
    b>Growth differentiation factor 15 (GDF-15) is the first cytokine known to counteract chemokine-induced activation of leukocyte integrins...
  37. Charalambous P, Wang X, Thanos S, Schober A, Unsicker K. Regulation and effects of GDF-15 in the retina following optic nerve crush. Cell Tissue Res. 2013;353:1-8 pubmed publisher
    ..GDF-15 is therefore prominently upregulated in the retina after optic nerve crush but does not directly interfere with the magnitude and temporal progression of RGC death. ..
  38. Choi H, Do K, Park J, Kim J, Yu M, Park S, et al. Early Epithelial Restitution by Nonsteroidal Anti-Inflammatory Drug-Activated Gene 1 Counteracts Intestinal Ulcerative Injuries. J Immunol. 2016;197:1415-24 pubmed publisher
  39. Li D, Zhang H, Zhong Y. Hepatic GDF15 is regulated by CHOP of the unfolded protein response and alleviates NAFLD progression in obese mice. Biochem Biophys Res Commun. 2018;498:388-394 pubmed publisher
    ..b>Growth differentiation factor 15 (GDF15) shows a broad range of effects on lipid homeostasis...
  40. Lee S, Kang S, Choi M, Jung S, Ryu M, Chung H, et al. Growth Differentiation Factor 15 Mediates Systemic Glucose Regulatory Action of T-Helper Type 2 Cytokines. Diabetes. 2017;66:2774-2788 pubmed publisher
    ..Recombinant IL-13 induced expression of growth differentiation factor 15 (GDF15) via the Janus kinase-activated STAT6 pathway...
  41. Kim D, Lee D, Chang E, Kim J, Hwang J, Kim J, et al. GDF-15 secreted from human umbilical cord blood mesenchymal stem cells delivered through the cerebrospinal fluid promotes hippocampal neurogenesis and synaptic activity in an Alzheimer's disease model. Stem Cells Dev. 2015;24:2378-90 pubmed publisher
  42. Machado V, Gilsbach R, Das R, Schober A, Bogatyreva L, Hauschke D, et al. Gdf-15 deficiency does not alter vulnerability of nigrostriatal dopaminergic system in MPTP-intoxicated mice. Cell Tissue Res. 2016;365:209-23 pubmed publisher
  43. Choi H, Kim J, Do K, Park S, Moon Y. Enteropathogenic Escherichia coli-induced macrophage inhibitory cytokine 1 mediates cancer cell survival: an in vitro implication of infection-linked tumor dissemination. Oncogene. 2013;32:4960-9 pubmed publisher
    ..We conclude that EPEC enhances MIC-1 gene expression in the human intestinal cancer cells, which can be associated with enhanced tumor cell resistance to anchorage-dependent tumor cell death via enhanced TAK1 and RhoA GTPase. ..
  44. Choi H, Kim H, Kim J, Park S, Park J, Oh C, et al. Pro-apoptotic action of macrophage inhibitory cytokine 1 and counteraction of activating transcription factor 3 in carrageenan-exposed enterocytes. Toxicol Lett. 2014;231:1-8 pubmed publisher
    ..These findings demonstrated that the counterbalance between MIC-1 and ATF3 is critical for deciding the fate of enterocytes under the food chemical stress. ..
  45. Carrillo García C, Prochnow S, Simeonova I, Strelau J, Hölzl Wenig G, Mandl C, et al. Growth/differentiation factor 15 promotes EGFR signalling, and regulates proliferation and migration in the hippocampus of neonatal and young adult mice. Development. 2014;141:773-83 pubmed publisher
    ..We also provide evidence that GDF15 promotes responsiveness to EGF and EGFR expression in hippocampal precursors through a mechanism that requires ..
  46. Chu M, Ahn V, Choi H, Daniels D, Nusse R, Weis W. structural Studies of Wnts and identification of an LRP6 binding site. Structure. 2013;21:1235-42 pubmed publisher
    ..Structure-based mutational analysis of mouse Wnt3a shows that the linker between the N- and C-terminal domains is required for LRP6 binding. These findings provide important insights into Wnt function and evolution. ..
  47. Chrysovergis K, Wang X, Kosak J, Lee S, Kim J, Foley J, et al. NAG-1/GDF-15 prevents obesity by increasing thermogenesis, lipolysis and oxidative metabolism. Int J Obes (Lond). 2014;38:1555-64 pubmed publisher
    ..hNAG-1 modulates metabolic activity by increasing the expression of key thermogenic and lipolytic genes in BAT and WAT. hNAG-1 appears to be a novel therapeutic target in preventing and treating obesity and insulin resistance. ..