GDF15

Summary

Gene Symbol: GDF15
Description: growth differentiation factor 15
Alias: GDF-15, MIC-1, MIC1, NAG-1, PDF, PLAB, PTGFB, growth/differentiation factor 15, NRG-1, NSAID (nonsteroidal anti-inflammatory drug)-activated protein 1, NSAID-activated gene 1 protein, NSAID-regulated gene 1 protein, PTGF-beta, macrophage inhibitory cytokine 1, non-steroidal anti-inflammatory drug-activated gene-1, placental TGF-beta, placental bone morphogenetic protein, prostate differentiation factor
Species: human
Products:     GDF15

Top Publications

  1. 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. ..
  2. Moore A, Brown D, Fairlie W, Bauskin A, Brown P, Munier M, et al. The transforming growth factor-ss superfamily cytokine macrophage inhibitory cytokine-1 is present in high concentrations in the serum of pregnant women. J Clin Endocrinol Metab. 2000;85:4781-8 pubmed
    ..We suggest that MIC-1 may promote fetal survival by suppressing the production of maternally derived proinflammatory cytokines within the uterus. ..
  3. Brown D, Breit S, Buring J, Fairlie W, Bauskin A, Liu T, et al. Concentration in plasma of macrophage inhibitory cytokine-1 and risk of cardiovascular events in women: a nested case-control study. Lancet. 2002;359:2159-63 pubmed
    ..There was no significant association between MIC-1 polymorphism and vascular events. MIC-1 could be a novel target for cardiovascular disease prevention. ..
  4. Brown D, Bauskin A, Fairlie W, Smith M, Liu T, Xu N, et al. Antibody-based approach to high-volume genotyping for MIC-1 polymorphism. Biotechniques. 2002;33:118-20, 122, 124 passim pubmed
    ..This novel antibody-based assay confidently determines the genotype of MIC-1. It offers the advantages of an ELISA-ease of automation, high-volume throughput of samples, and ease of use in a routine, clinical laboratory. ..
  5. Shim M, Eling T. Protein kinase C-dependent regulation of NAG-1/placental bone morphogenic protein/MIC-1 expression in LNCaP prostate carcinoma cells. J Biol Chem. 2005;280:18636-42 pubmed
    ..These results demonstrate that NAG-1 expression is up-regulated by TPA in LNCaP cells through a PKC-dependent pathway involving the activation of NF-kappa B. ..
  6. Wang X, Yang X, Sun K, Chen J, Song X, Wang H, et al. The haplotype of the growth-differentiation factor 15 gene is associated with left ventricular hypertrophy in human essential hypertension. Clin Sci (Lond). 2009;118:137-45 pubmed publisher
    b>GDF15 (growth-differentiation factor 15) is a novel antihypertrophic factor which is induced in the heart in response to pressure overload and plays an important regulatory role in the process of hypertrophy...
  7. Eggers K, Kempf T, Lind L, Sundstrom J, Wallentin L, Wollert K, et al. Relations of growth-differentiation factor-15 to biomarkers reflecting vascular pathologies in a population-based sample of elderly subjects. Scand J Clin Lab Invest. 2012;72:45-51 pubmed publisher
    ..In the elderly, GDF-15 reflects endothelial activation and vascular inflammation and thus, multiple pathways involved in the development and progression of atherosclerosis. ..
  8. Yokoyama Kobayashi M, Saeki M, Sekine S, Kato S. Human cDNA encoding a novel TGF-beta superfamily protein highly expressed in placenta. J Biochem. 1997;122:622-6 pubmed
    ..The corresponding transcripts are highly expressed in the placenta, so the novel protein may play an important role in reproduction. ..
  9. Boyle G, Pedley J, Martyn A, Banducci K, Strutton G, Brown D, et al. Macrophage inhibitory cytokine-1 is overexpressed in malignant melanoma and is associated with tumorigenicity. J Invest Dermatol. 2009;129:383-91 pubmed publisher
    ..These results indicate that MIC-1 may function to promote development of more aggressive melanoma tumors. MIC-1 may be suitable for development as a serum diagnostic and is a possible target for the treatment of metastatic melanoma. ..

More Information

Publications71

  1. Nickel N, Jonigk D, Kempf T, Bockmeyer C, Maegel L, Rische J, et al. GDF-15 is abundantly expressed in plexiform lesions in patients with pulmonary arterial hypertension and affects proliferation and apoptosis of pulmonary endothelial cells. Respir Res. 2011;12:62 pubmed publisher
    ..The expression pattern as well as the observed effects on proliferation and apoptosis of pulmonary endothelial cells suggest a role of GDF-15 in the homeostasis of endothelial cells in PAH patients. ..
  2. Khan S, Ng K, Dhillon O, Kelly D, Quinn P, Squire I, et al. Growth differentiation factor-15 as a prognostic marker in patients with acute myocardial infarction. Eur Heart J. 2009;30:1057-65 pubmed publisher
    ..GDF-15 provides prognostic information over and above clinical factors and the established biomarker NT-proBNP. Combined levels of GDF-15 with NT-proBNP can identify a high-risk group of patients. ..
  3. Joshi J, Brown N, Griner S, Nahta R. Growth differentiation factor 15 (GDF15)-mediated HER2 phosphorylation reduces trastuzumab sensitivity of HER2-overexpressing breast cancer cells. Biochem Pharmacol. 2011;82:1090-9 pubmed publisher
    ..b>Growth differentiation factor 15 (GDF15), which is structurally similar to TGF beta, has been reported to stimulate phosphorylation of ..
  4. Tamary H, Shalev H, Perez Avraham G, Zoldan M, Levi I, Swinkels D, et al. Elevated growth differentiation factor 15 expression in patients with congenital dyserythropoietic anemia type I. Blood. 2008;112:5241-4 pubmed publisher
    ..To determine whether growth differentation factor 15 (GDF15) hyper-expression is associated with the ineffective erythropoiesis and iron-loading complications of CDA type I (..
  5. Strelau J, Sullivan A, Bottner M, Lingor P, Falkenstein E, Suter Crazzolara C, et al. Growth/differentiation factor-15/macrophage inhibitory cytokine-1 is a novel trophic factor for midbrain dopaminergic neurons in vivo. J Neurosci. 2000;20:8597-603 pubmed
    ..Thus, GDF-15/MIC-1 is a novel neurotrophic factor with prominent effects on DAergic and serotonergic neurons. GDF-15/MIC-1 may therefore have a potential for the treatment of Parkinson's disease and disorders of the serotonergic system. ..
  6. Fairlie W, Russell P, Wu W, Moore A, Zhang H, Brown P, et al. Epitope mapping of the transforming growth factor-beta superfamily protein, macrophage inhibitory cytokine-1 (MIC-1): identification of at least five distinct epitope specificities. Biochemistry. 2001;40:65-73 pubmed
    ..Finally, the use of another mutant in which Cys 77 was replaced by serine enabled confirmation of the location of the MIC-1 interchain disulfide bond. ..
  7. Bonaca M, Morrow D, Braunwald E, Cannon C, Jiang S, Breher S, et al. Growth differentiation factor-15 and risk of recurrent events in patients stabilized after acute coronary syndrome: observations from PROVE IT-TIMI 22. Arterioscler Thromb Vasc Biol. 2011;31:203-10 pubmed publisher
    ..This finding supports GDF-15 as a prognostic marker in ACS and investigation of other therapies that modify this risk. ..
  8. Brown D, Moore J, Johnen H, Smeets T, Bauskin A, Kuffner T, et al. Serum macrophage inhibitory cytokine 1 in rheumatoid arthritis: a potential marker of erosive joint destruction. Arthritis Rheum. 2007;56:753-64 pubmed
    The transforming growth factor beta superfamily member macrophage inhibitory cytokine 1 (MIC-1) is expressed upon macrophage activation, regulated by the p53 pathway, and linked to clinical events in atherosclerosis and cancer...
  9. Akiyama M, Okano K, Fukada Y, Okano T. Macrophage inhibitory cytokine MIC-1 is upregulated by short-wavelength light in cultured normal human dermal fibroblasts. FEBS Lett. 2009;583:933-7 pubmed publisher
    ..Considering the role of MIC-1 in immune regulation and appetite control, photic MIC-1 regulation is of physiological importance. ..
  10. Lajer M, Jorsal A, Tarnow L, Parving H, Rossing P. Plasma growth differentiation factor-15 independently predicts all-cause and cardiovascular mortality as well as deterioration of kidney function in type 1 diabetic patients with nephropathy. Diabetes Care. 2010;33:1567-72 pubmed publisher
    ..Higher levels of GDF-15 are a predictor of all-cause and cardiovascular mortality and morbidity in patients with diabetic nephropathy. Furthermore, higher levels of GDF-15 are associated with faster deterioration of kidney function. ..
  11. Kadowaki M, Yoshioka H, Kamitani H, Watanabe T, Wade P, Eling T. DNA methylation-mediated silencing of nonsteroidal anti-inflammatory drug-activated gene (NAG-1/GDF15) in glioma cell lines. Int J Cancer. 2012;130:267-77 pubmed publisher
    ..We concluded from these data that methylation of specific promoter sequences causes transcriptional silencing of the NAG-1 locus in glioma and may ultimately contribute to tumor progression. ..
  12. Senapati S, Rachagani S, Chaudhary K, Johansson S, Singh R, Batra S. Overexpression of macrophage inhibitory cytokine-1 induces metastasis of human prostate cancer cells through the FAK-RhoA signaling pathway. Oncogene. 2010;29:1293-302 pubmed publisher
    ..Activation of the FAK-RhoA signaling pathway is involved in MIC-1-mediated actin reorganization, and thus, leads to an increase in the motility of prostate cancer cells. ..
  13. Kempf T, Sinning J, Quint A, Bickel C, Sinning C, Wild P, et al. Growth-differentiation factor-15 for risk stratification in patients with stable and unstable coronary heart disease: results from the AtheroGene study. Circ Cardiovasc Genet. 2009;2:286-92 pubmed publisher
    ..This study identifies GDF-15 as a strong and independent predictor of CHD mortality across the broad spectrum of patients with stable and unstable CHD. ..
  14. Song H, Yin D, Liu Z. GDF-15 promotes angiogenesis through modulating p53/HIF-1? signaling pathway in hypoxic human umbilical vein endothelial cells. Mol Biol Rep. 2012;39:4017-22 pubmed publisher
    ..Previous studies suggested that growth differentiation factor 15 (GDF-15) was one of the most important factors responsible for promoting the angiogenesis process ..
  15. Welsh J, Sapinoso L, Kern S, Brown D, Liu T, Bauskin A, et al. Large-scale delineation of secreted protein biomarkers overexpressed in cancer tissue and serum. Proc Natl Acad Sci U S A. 2003;100:3410-5 pubmed
    ..microarrays and further demonstrate significantly elevated levels of another novel candidate protein, macrophage inhibitory cytokine 1, a distant member of the transforming growth factor-beta superfamily, in the serum of patients with ..
  16. Bootcov M, Bauskin A, Valenzuela S, Moore A, Bansal M, He X, et al. MIC-1, a novel macrophage inhibitory cytokine, is a divergent member of the TGF-beta superfamily. Proc Natl Acad Sci U S A. 1997;94:11514-9 pubmed
    ..One of these genes, designated macrophage inhibitory cytokine 1 (MIC-1), encodes a protein that bears the structural characteristics of a transforming growth factor ..
  17. Wakchoure S, Swain T, Hentunen T, Bauskin A, Brown D, Breit S, et al. Expression of macrophage inhibitory cytokine-1 in prostate cancer bone metastases induces osteoclast activation and weight loss. Prostate. 2009;69:652-61 pubmed publisher
    ..MIC-1 stimulates both osteoblast and osteoclast differentiation in vitro, independently of TLR9. MIC-1 over-expressing prostate cancer cells that grow in bone induce osteoclast formation and cachexia. ..
  18. 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. ..
  19. Wiklund F, Bennet A, Magnusson P, Eriksson U, Lindmark F, Wu L, et al. Macrophage inhibitory cytokine-1 (MIC-1/GDF15): a new marker of all-cause mortality. Aging Cell. 2010;9:1057-64 pubmed publisher
    Macrophage inhibitory cytokine-1 (MIC-1/GDF15) is a member of the TGF-b superfamily, previously studied in cancer and inflammation...
  20. Suesskind D, Schatz A, Schnichels S, Coupland S, Lake S, Wissinger B, et al. GDF-15: a novel serum marker for metastases in uveal melanoma patients. Graefes Arch Clin Exp Ophthalmol. 2012;250:887-95 pubmed publisher
    ..Further data collection and analysis are necessary to evaluate a possible prognostic role of GDF-15 in predicting early metastases. ..
  21. Vanhara P, Lincová E, Kozubik A, Jurdic P, Soucek K, Smarda J. Growth/differentiation factor-15 inhibits differentiation into osteoclasts--a novel factor involved in control of osteoclast differentiation. Differentiation. 2009;78:213-22 pubmed publisher
    ..These results unveil new role of GDF-15 in modulation of osteoclast differentiation and possibly in therapy of bone metastases. ..
  22. Hellemons M, Mazagova M, Gansevoort R, Henning R, de Zeeuw D, Bakker S, et al. Growth-differentiation factor 15 predicts worsening of albuminuria in patients with type 2 diabetes. Diabetes Care. 2012;35:2340-6 pubmed publisher
    ..In addition, we looked at the GDF-15 potential in nondiabetic subjects with hypertension (HT)...
  23. 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. ..
  24. Bock A, Stavnes H, Kempf T, Trope C, Berner A, Davidson B, et al. Expression and clinical role of growth differentiation factor-15 in ovarian carcinoma effusions. Int J Gynecol Cancer. 2010;20:1448-55 pubmed publisher
    ..Growth differentiation factor-15 emerges as a potential prognostic biomarker in ovarian carcinoma. ..
  25. Li P, Wong J, Ayed A, Ngo D, Brade A, Arrowsmith C, et al. Placental transforming growth factor-beta is a downstream mediator of the growth arrest and apoptotic response of tumor cells to DNA damage and p53 overexpression. J Biol Chem. 2000;275:20127-35 pubmed
  26. Carstensen M, Herder C, Brunner E, Strassburger K, Tabak A, Roden M, et al. Macrophage inhibitory cytokine-1 is increased in individuals before type 2 diabetes diagnosis but is not an independent predictor of type 2 diabetes: the Whitehall II study. Eur J Endocrinol. 2010;162:913-7 pubmed publisher
    ..This upregulation of MIC-1 could be part of an anti-inflammatory response preceding the onset of type 2 diabetes, which has been described before for interleukin-1 receptor antagonist and TGF-beta1. ..
  27. Anand I, Kempf T, Rector T, Tapken H, Allhoff T, Jantzen F, et al. Serial measurement of growth-differentiation factor-15 in heart failure: relation to disease severity and prognosis in the Valsartan Heart Failure Trial. Circulation. 2010;122:1387-95 pubmed publisher
    ..GDF-15 levels increase over time, suggesting that GDF-15 reflects a pathophysiological axis that is not completely addressed by the therapies prescribed in Val-HeFT. ..
  28. Ichikawa T, Suenaga Y, Koda T, Ozaki T, Nakagawara A. TAp63-dependent induction of growth differentiation factor 15 (GDF15) plays a critical role in the regulation of keratinocyte differentiation. Oncogene. 2008;27:409-20 pubmed
    ..we have found that TAp63alpha is induced in association with the upregulation and a secretion of growth differentiation factor 15 (GDF15) during the keratinocyte differentiation of HaCaT cells bearing p53 mutation...
  29. 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. ..
  30. 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...
  31. Lawton L, Bonaldo M, Jelenc P, Qiu L, Baumes S, Marcelino R, et al. Identification of a novel member of the TGF-beta superfamily highly expressed in human placenta. Gene. 1997;203:17-26 pubmed
    ..Hence, we named this factor 'Placental Transforming Growth Factor Beta' (PTGFB). The full-length sequence of the 1...
  32. Baek S, Horowitz J, Eling T. Molecular cloning and characterization of human nonsteroidal anti-inflammatory drug-activated gene promoter. Basal transcription is mediated by Sp1 and Sp3. J Biol Chem. 2001;276:33384-92 pubmed
    ..Furthermore, the results suggest that the level of expression of the NAG-1 gene will depend on the availability of Sp proteins and on co-factors such as chicken ovalbumin upstream promoter-transcription factor 1. ..
  33. Johnen H, Lin S, Kuffner T, Brown D, Tsai V, Bauskin A, et al. Tumor-induced anorexia and weight loss are mediated by the TGF-beta superfamily cytokine MIC-1. Nat Med. 2007;13:1333-40 pubmed
    ..Thus, MIC-1 is a newly defined central regulator of appetite and a potential target for the treatment of both cancer anorexia and weight loss, as well as of obesity. ..
  34. Hromas R, Hufford M, Sutton J, Xu D, Li Y, Lu L. PLAB, a novel placental bone morphogenetic protein. Biochim Biophys Acta. 1997;1354:40-4 pubmed
    ..We have recently isolated a novel member of the BMP family from placenta, termed PLAB. PLAB is expressed highly in placenta, but can be found upon stringent analysis in low levels in most other tissues...
  35. 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. ..
  36. Huang C, Beer T, Higano C, True L, Vessella R, Lange P, et al. Molecular alterations in prostate carcinomas that associate with in vivo exposure to chemotherapy: identification of a cytoprotective mechanism involving growth differentiation factor 15. Clin Cancer Res. 2007;13:5825-33 pubmed
    ..In vitro analyses determining the influence of growth differentiation factor 15 (GDF15) on chemotherapy resistance were done...
  37. Corre J, Labat E, Espagnolle N, Hébraud B, Avet Loiseau H, Roussel M, et al. Bioactivity and prognostic significance of growth differentiation factor GDF15 secreted by bone marrow mesenchymal stem cells in multiple myeloma. Cancer Res. 2012;72:1395-406 pubmed publisher
    Overexpression of growth differentiation factor 15 (GDF15) by bone marrow mesenchymal stem cells occurs widely in patients with multiple myeloma, but the pathophysiologic effects of GDF15 in this setting remain undefined...
  38. Liu T, Bauskin A, Zaunders J, Brown D, Pankhurst S, Russell P, et al. Macrophage inhibitory cytokine 1 reduces cell adhesion and induces apoptosis in prostate cancer cells. Cancer Res. 2003;63:5034-40 pubmed
    b>Macrophage inhibitory cytokine 1 (MIC-1), a divergent member of the transforming growth factor-beta superfamily, is linked to the pathogenesis of cancer...
  39. Koopmann J, Buckhaults P, Brown D, Zahurak M, Sato N, Fukushima N, et al. Serum macrophage inhibitory cytokine 1 as a marker of pancreatic and other periampullary cancers. Clin Cancer Res. 2004;10:2386-92 pubmed
    ..05; area under the receiver operating characteristic curve, 0.87; sensitivity, 70%; specificity, 85%). Serum MIC-1 measurement can aid in the diagnosis of pancreatic adenocarcinoma. ..
  40. Lee S, Kim J, Yamaguchi K, Eling T, Baek S. Indole-3-carbinol and 3,3'-diindolylmethane induce expression of NAG-1 in a p53-independent manner. Biochem Biophys Res Commun. 2005;328:63-9 pubmed
    ..Furthermore, the mixture of I3C with resveratrol enhances NAG-1 expression, suggesting the synergistic effect of these two unrelated compounds on NAG-1 expression. ..
  41. Dostalova I, Roubicek T, Bartlova M, Mraz M, Lacinova Z, Haluzikova D, et al. Increased serum concentrations of macrophage inhibitory cytokine-1 in patients with obesity and type 2 diabetes mellitus: the influence of very low calorie diet. Eur J Endocrinol. 2009;161:397-404 pubmed publisher
    ..We suggest that in contrast to patients with cancer cachexia, increased MIC-1 levels in obese patients and diabetic patients do not induce weight loss. ..
  42. Ago T, Sadoshima J. GDF15, a cardioprotective TGF-beta superfamily protein. Circ Res. 2006;98:294-7 pubmed
  43. Baek K, Yoon S, Kim J, Kim K, Kang S, Yang Y, et al. Upregulation and secretion of macrophage inhibitory cytokine-1 (MIC-1) in gastric cancers. Clin Chim Acta. 2009;401:128-33 pubmed publisher
    ..MIC-1 was obviously overexpressed in gastric cancers and MIC-1 secretion into blood may be useful for the prediction of gastric cancer progression. ..
  44. Brown D, Hance K, Rogers C, Sansbury L, Albert P, Murphy G, et al. Serum macrophage inhibitory cytokine-1 (MIC-1/GDF15): a potential screening tool for the prevention of colon cancer?. Cancer Epidemiol Biomarkers Prev. 2012;21:337-46 pubmed publisher
    Macrophage inhibitory cytokine-1 (MIC-1/GDF15) mediates nonsteroidal anti-inflammatory drug (NSAID) protection from colonic polyps in mice and is linked to the development of colorectal carcinoma in humans...
  45. Soucek K, Slabáková E, Ovesna P, Malenovská A, Kozubik A, Hampl A. Growth/differentiation factor-15 is an abundant cytokine in human seminal plasma. Hum Reprod. 2010;25:2962-71 pubmed publisher
    ..Moreover, our data show that GDF-15 displays immunosuppressive characteristics. ..
  46. Kelly J, Lucia M, Lambert J. p53 controls prostate-derived factor/macrophage inhibitory cytokine/NSAID-activated gene expression in response to cell density, DNA damage and hypoxia through diverse mechanisms. Cancer Lett. 2009;277:38-47 pubmed publisher
    ..Here, we demonstrate that the TGF-beta superfamily member, and putative tumor suppressor, prostate-derived factor (PDF)/NSAID-activated gene (NAG)-1/macrophage inhibitory cytokine (MIC)-1 is induced in LNCaP human prostate cancer ..
  47. Albertoni M, Shaw P, Nozaki M, Godard S, Tenan M, Hamou M, et al. Anoxia induces macrophage inhibitory cytokine-1 (MIC-1) in glioblastoma cells independently of p53 and HIF-1. Oncogene. 2002;21:4212-9 pubmed
    ..Taken together, these data suggest that MIC-1 is an important downstream mediator of p53 function, while acting itself as an intercessor of cellular stress signaling and exerting anti-tumorigenic activities. ..
  48. Eggers K, Kempf T, Lagerqvist B, Lindahl B, Olofsson S, Jantzen F, et al. Growth-differentiation factor-15 for long-term risk prediction in patients stabilized after an episode of non-ST-segment-elevation acute coronary syndrome. Circ Cardiovasc Genet. 2010;3:88-96 pubmed publisher
    ..Therefore, continued research on GDF-15 should be focused on the usefulness of GDF-15 for support of clinical management in acute and chronic ischemic heart disease. ..
  49. Kempf T, Wollert K. Growth differentiation factor-15: a new biomarker in cardiovascular disease. Herz. 2009;34:594-9 pubmed publisher
    ..Future studies need to evaluate prospectively whether GDF-15, alone or as part of a multimarker strategy, can improve contemporary risk prediction algorithms and support therapeutic management of patients with cardiovascular disease. ..
  50. 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. ..
  51. Strelau J, Schmeer C, Peterziel H, Sackmann T, Herold Mende C, Steiner H, et al. Expression and putative functions of GDF-15, a member of the TGF-beta superfamily, in human glioma and glioblastoma cell lines. Cancer Lett. 2008;270:30-9 pubmed publisher
  52. Tong S, Marjono B, Brown D, Mulvey S, Breit S, Manuelpillai U, et al. Serum concentrations of macrophage inhibitory cytokine 1 (MIC 1) as a predictor of miscarriage. Lancet. 2004;363:129-30 pubmed
    b>Macrophage inhibitory cytokine 1 (MIC 1) is thought to have immunomodulatory actions favouring fetal viability...
  53. Paralkar V, Vail A, Grasser W, Brown T, Xu H, Vukicevic S, et al. Cloning and characterization of a novel member of the transforming growth factor-beta/bone morphogenetic protein family. J Biol Chem. 1998;273:13760-7 pubmed
    ..expressed at high levels in the placenta and the prostate and that we have designated as prostate-derived factor (PDF)...
  54. Shnaper S, Desbaillets I, Brown D, Murat A, Migliavacca E, Schluep M, et al. Elevated levels of MIC-1/GDF15 in the cerebrospinal fluid of patients are associated with glioblastoma and worse outcome. Int J Cancer. 2009;125:2624-30 pubmed publisher
    ..MIC-1/GDF15 (growth differentiation factor 15) is a secreted protein of the TGF-beta superfamily and emerged as a candidate marker exhibiting ..
  55. Tanno T, Bhanu N, Oneal P, Goh S, Staker P, Lee Y, et al. High levels of GDF15 in thalassemia suppress expression of the iron regulatory protein hepcidin. Nat Med. 2007;13:1096-101 pubmed
    ..b>Growth differentiation factor 15 (GDF15), a member of the transforming growth factor-beta superfamily, showed increased expression and ..
  56. Baek S, Kim K, Nixon J, Wilson L, Eling T. Cyclooxygenase inhibitors regulate the expression of a TGF-beta superfamily member that has proapoptotic and antitumorigenic activities. Mol Pharmacol. 2001;59:901-8 pubmed
    ..These data demonstrate that NAG-1 is an antitumorigenic and proapoptotic protein, and its regulation by COX inhibitors may provide new clues for explaining their proapoptotic and antitumorigenic activities. ..
  57. Bloch S, Lee J, Wort S, Polkey M, Kemp P, Griffiths M. Sustained elevation of circulating growth and differentiation factor-15 and a dynamic imbalance in mediators of muscle homeostasis are associated with the development of acute muscle wasting following cardiac surgery. Crit Care Med. 2013;41:982-9 pubmed publisher
    ..Growth and differentiation factor-15 is a potential novel factor associated with muscle atrophy, which may become a therapeutic target in patients with ICU acquired paresis and other forms of acute muscle wasting. ..
  58. 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...
  59. Li J, Yang L, Qin W, Zhang G, Yuan J, Wang F. Adaptive induction of growth differentiation factor 15 attenuates endothelial cell apoptosis in response to high glucose stimulus. PLoS ONE. 2013;8:e65549 pubmed publisher
    b>Growth differentiation factor 15 (GDF15), a direct target gene of p53, is a multifunctional member of the TGF-?/BMP superfamily. GDF15 can be induced and is implicated as a key secretory cytokine in response to multiple cellular stimuli...
  60. Brown D, Ward R, Buckhaults P, Liu T, Romans K, Hawkins N, et al. MIC-1 serum level and genotype: associations with progress and prognosis of colorectal carcinoma. Clin Cancer Res. 2003;9:2642-50 pubmed
    ..We suggest that the measurement of serum MIC-1 levels and determination of MIC-1 genotype may have clinical use in the management of patients with CRC. ..
  61. Staff A, Bock A, Becker C, Kempf T, Wollert K, Davidson B. Growth differentiation factor-15 as a prognostic biomarker in ovarian cancer. Gynecol Oncol. 2010;118:237-43 pubmed publisher
    ..01). GDF-15 protein was cytoplasmatically expressed in serous tumor cells and detectable in high concentrations in effusion samples. GDF-15 emerges as a new potential biomarker in ovarian cancer. ..
  62. Segerer S, Rieger L, Kapp M, Dombrowski Y, Muller N, Dietl J, et al. MIC-1 (a multifunctional modulator of dendritic cell phenotype and function) is produced by decidual stromal cells and trophoblasts. Hum Reprod. 2012;27:200-9 pubmed publisher
    ..So far, little is known about the decidual cell subsets producing MIC-1 and the effect of this cytokine on dendritic cells (DCs), which are known to play a distinct role in the development of pro-fetal tolerance in pregnancy...