Gene Symbol: Mdk
Description: midkine
Alias: Mek, midkine, retinoic acid-induced differentiation factor, retinoic acid-responsive protein
Species: mouse
Products:     Mdk

Top Publications

  1. Maruyama K, Muramatsu H, Ishiguro N, Muramatsu T. Midkine, a heparin-binding growth factor, is fundamentally involved in the pathogenesis of rheumatoid arthritis. Arthritis Rheum. 2004;50:1420-9 pubmed
    b>Midkine (MK), a heparin-binding growth factor, promotes growth, survival, and migration of various cells. The essential role of MK in migration of inflammatory cells has been shown using mice deficient in the MK gene (Mdk(-/-) mice)...
  2. Muramatsu T. Midkine (MK), the product of a retinoic acid responsive gene, and pleiotrophin constitute a new protein family regulating growth and differentiation. Int J Dev Biol. 1993;37:183-8 pubmed
    Using mouse teratocarcinoma system, we found a novel retinoic acid responsive gene. Midkine (MK), the product of the gene is a secreted, heparin-binding protein of molecular weight 14,000...
  3. Michikawa M, Kikuchi S, Muramatsu H, Muramatsu T, Kim S. Retinoic acid responsive gene product, midkine, has neurotrophic functions for mouse spinal cord and dorsal root ganglion neurons in culture. J Neurosci Res. 1993;35:530-9 pubmed
    b>Midkine (MK) is the product of a retinoic acid responsive gene and is a member of a new family of heparin-binding growth factors...
  4. Wang J, Takeuchi H, Sonobe Y, Jin S, Mizuno T, Miyakawa S, et al. Inhibition of midkine alleviates experimental autoimmune encephalomyelitis through the expansion of regulatory T cell population. Proc Natl Acad Sci U S A. 2008;105:3915-20 pubmed publisher
    ..The factors that regulate Treg cells, however, are largely unknown. Here, we show that deficiency in midkine (MK), a heparin-binding growth factor involved in oncogenesis, inflammation, and tissue repair, attenuated ..
  5. Weckbach L, Groesser L, Borgolte J, Pagel J, Pogoda F, Schymeinsky J, et al. Midkine acts as proangiogenic cytokine in hypoxia-induced angiogenesis. Am J Physiol Heart Circ Physiol. 2012;303:H429-38 pubmed publisher
    The cytokine midkine (MK) promotes tumor growth mainly by inducing angiogenesis. Here, we identified the source of MK in the vascular system under hypoxic conditions and demonstrated the relevance of MK during ischemia of normal tissue...
  6. Cernkovich E, Deng J, Hua K, Harp J. Midkine is an autocrine activator of signal transducer and activator of transcription 3 in 3T3-L1 cells. Endocrinology. 2007;148:1598-604 pubmed
    ..We further determined that the factor has heparin binding properties and identified the factor as midkine, a pleiotrophic growth factor previously associated with neuronal development and oncogenesis...
  7. Horiba M, Kadomatsu K, Nakamura E, Muramatsu H, Ikematsu S, Sakuma S, et al. Neointima formation in a restenosis model is suppressed in midkine-deficient mice. J Clin Invest. 2000;105:489-95 pubmed
    ..To find a new target to suppress neointima formation, we investigated the possible role of midkine (MK), a heparin-binding growth factor with neurotrophic and chemotactic activities, in neointima formation...
  8. Ezquerra L, Herradon G, Nguyen T, Silos Santiago I, Deuel T. Midkine, a newly discovered regulator of the renin-angiotensin pathway in mouse aorta: significance of the pleiotrophin/midkine developmental gene family in angiotensin II signaling. Biochem Biophys Res Commun. 2005;333:636-43 pubmed
    ..the levels of expression of these same genes are significantly regulated in mouse aorta by the PTN family member midkine (MK the protein, Mk the gene); a 3-fold increase in expression of renin, an 82-fold increase in angiotensinogen, ..
  9. Kadomatsu K, Tomomura M, Muramatsu T. cDNA cloning and sequencing of a new gene intensely expressed in early differentiation stages of embryonal carcinoma cells and in mid-gestation period of mouse embryogenesis. Biochem Biophys Res Commun. 1988;151:1312-8 pubmed
    ..The corresponding RNA was 1.0 killobase in size. From the nucleotide sequence, MK1 gene was predicted to code a polypeptide of molecular weight 9,971, which was rich in basic amino acids. ..

More Information


  1. Stoica G, Kuo A, Powers C, Bowden E, Sale E, Riegel A, et al. Midkine binds to anaplastic lymphoma kinase (ALK) and acts as a growth factor for different cell types. J Biol Chem. 2002;277:35990-8 pubmed
    b>Midkine (MK) is a developmentally regulated, secreted growth factor homologous to pleiotrophin (PTN)...
  2. Lovgren A, Kovarova M, Koller B. cPGES/p23 is required for glucocorticoid receptor function and embryonic growth but not prostaglandin E2 synthesis. Mol Cell Biol. 2007;27:4416-30 pubmed
  3. Igakura T, Kadomatsu K, Kaname T, Muramatsu H, Fan Q, Miyauchi T, et al. A null mutation in basigin, an immunoglobulin superfamily member, indicates its important roles in peri-implantation development and spermatogenesis. Dev Biol. 1998;194:152-65 pubmed
    ..In conclusion, basigin is an important cell-surface molecule involved in early embryogenesis and reproduction. ..
  4. Goettel J, Liang D, Hilliard V, Edelblum K, Broadus M, Gould K, et al. KSR1 is a functional protein kinase capable of serine autophosphorylation and direct phosphorylation of MEK1. Exp Cell Res. 2011;317:452-63 pubmed publisher
    ..However, +KSR1 cells were sensitized to TNF-induced cell loss in the absence of MEK kinase activity...
  5. Hobo A, Yuzawa Y, Kosugi T, Kato N, Asai N, Sato W, et al. The growth factor midkine regulates the renin-angiotensin system in mice. J Clin Invest. 2009;119:1616-25 pubmed publisher
    ..Here, we report that the growth factor midkine is what we believe to be a novel regulator of the renin-angiotensin system...
  6. Ishikawa E, Ooboshi H, Kumai Y, Takada J, Nakamura K, Ago T, et al. Midkine gene transfer protects against focal brain ischemia and augments neurogenesis. J Neurol Sci. 2009;285:78-84 pubmed publisher
    b>Midkine is a heparin-binding growth factor having various biological activities including chemotaxis of inflammatory cells, angiogenesis and migration of neuronal cells...
  7. Neunaber C, Catala Lehnen P, Beil F, Marshall R, Kanbach V, Baranowsky A, et al. Increased trabecular bone formation in mice lacking the growth factor midkine. J Bone Miner Res. 2010;25:1724-35 pubmed publisher
    b>Midkine (Mdk) and pleiotrophin (Ptn) comprise a family of heparin-binding growth factors known primarily for their effects on neuronal cells...
  8. Vicente Rodríguez M, Gramage E, Herradon G, Perez Garcia C. Phosphoproteomic analysis of the striatum from pleiotrophin knockout and midkine knockout mice treated with cocaine reveals regulation of oxidative stress-related proteins potentially underlying cocaine-induced neurotoxicity and neurodegeneration. Toxicology. 2013;314:166-73 pubmed publisher
    The neurotrophic factors pleiotrophin (PTN) and midkine (MK) are highly upregulated in different brain areas relevant to drug addiction after administrations of different drugs of abuse, including psychostimulants...
  9. Cohen S, Shoshana O, Zelman Toister E, Maharshak N, Binsky Ehrenreich I, Gordin M, et al. The cytokine midkine and its receptor RPTP? regulate B cell survival in a pathway induced by CD74. J Immunol. 2012;188:259-69 pubmed publisher
    ..peripheral mature B cells and chronic lymphocytic leukemia cells, regulated by the heparin-binding cytokine, midkine (MK), and its proteoglycan receptor, the receptor-type tyrosine phosphatase ? (RPTP?)...
  10. Chen P, Wakimoto H, Conner D, Araki T, Yuan T, Roberts A, et al. Activation of multiple signaling pathways causes developmental defects in mice with a Noonan syndrome–associated Sos1 mutation. J Clin Invest. 2010;120:4353-65 pubmed publisher
    ..Furthermore, prenatal administration of a MEK inhibitor ameliorated the embryonic lethality, cardiac defects, and NS features of the homozygous mutant mice, ..
  11. Reynolds P, Mucenski M, Le Cras T, Nichols W, Whitsett J. Midkine is regulated by hypoxia and causes pulmonary vascular remodeling. J Biol Chem. 2004;279:37124-32 pubmed
    b>Midkine (MK) is expressed in a precise temporal-spatial pattern during lung morphogenesis; however, its role in pulmonary homeostasis is unknown...
  12. Matsubara S, Take M, Pedraza C, Muramatsu T. Mapping and characterization of a retinoic acid-responsive enhancer of midkine, a novel heparin-binding growth/differentiation factor with neurotrophic activity. J Biochem. 1994;115:1088-96 pubmed
    ..b>Midkine, the product of the gene is a novel heparin-binding growth/differentiation factor with neurite outgrowth and ..
  13. Fan Q, Muramatsu T, Kadomatsu K. Distinct expression of midkine and pleiotrophin in the spinal cord and placental tissues during early mouse development. Dev Growth Differ. 2000;42:113-9 pubmed
    b>Midkine and pleiotrophin comprise a family of heparin-binding growth factors, and are expressed in overlapping tissues during the mid- to late-gestation periods of mouse development...
  14. O HARA B, Jenkins N, Gilbert D, Copeland N, Shows T, Eddy R, et al. Chromosomal assignment of the heparin-binding cytokine genes MDK and PTN in mouse and man. Cytogenet Cell Genet. 1995;69:40-3 pubmed
    b>MDK and PTN are two members of a family of heparin-binding cytokines thought to be involved in a number of developmental processes...
  15. Vicente Rodríguez M, Perez Garcia C, Gramage E, Herradon G. Genetic inactivation of pleiotrophin but not midkine potentiates clonidine-induced alpha-2 adrenergic-mediated analgesia. Pharmacol Biochem Behav. 2013;110:185-91 pubmed publisher
    Genetic deletion of the heparin-binding cytokines pleiotrophin (PTN) or midkine (MK) potentiates morphine-induced antinociceptive effects in animal models...
  16. Sato W, Yuzawa Y, Kadomatsu K, Tayasu T, Muramatsu H, Muramatsu T, et al. Midkine expression in the course of nephrogenesis and its role in ischaemic reperfusion injury. Nephrol Dial Transplant. 2002;17 Suppl 9:52-4 pubmed
    b>Midkine (MK) is a multifunctional heparin-binding growth factor with migration-promoting activity for neutrophils, macrophages and neurones...
  17. Cheng L, Qiao Z, Xu C, Shen J. Midkine is overexpressed in acute pancreatitis and promotes the pancreatic recovery in L-arginine-induced acute pancreatitis in mice. J Gastroenterol Hepatol. 2017;32:1265-1272 pubmed publisher
    b>Midkine (MK) is involved in the pathogenesis of numerous malignancies, but the expression and effect of MK in acute pancreatitis (AP) have not been well studied and documented...
  18. Kishida S, Mu P, Miyakawa S, Fujiwara M, Abe T, Sakamoto K, et al. Midkine promotes neuroblastoma through Notch2 signaling. Cancer Res. 2013;73:1318-27 pubmed publisher
    b>Midkine is a heparin-binding growth factor highly expressed in various cancers, including neuroblastoma, the most common extracranial pediatric solid tumor...
  19. Sato W, Sato Y. Midkine in nephrogenesis, hypertension and kidney diseases. Br J Pharmacol. 2014;171:879-87 pubmed publisher
    b>Midkine (MK; K; gene abbreviation, Mdk: mus musculus, MDK: homo sapiens) is a multifunctional heparin-binding growth factor that regulates cell growth, survival and migration as well as anti-apoptotic activity in nephrogenesis and ..
  20. Kosugi T, Yuzawa Y, Sato W, Arata Kawai H, Suzuki N, Kato N, et al. Midkine is involved in tubulointerstitial inflammation associated with diabetic nephropathy. Lab Invest. 2007;87:903-13 pubmed
    ..Here, we identified the growth factor midkine (MK) as a novel key molecule involved in inflammation associated with Streptozotocin-induced diabetic nephropathy...
  21. Yang Y, Wang Y, Lam K, Yau M, Cheng K, Zhang J, et al. Suppression of the Raf/MEK/ERK signaling cascade and inhibition of angiogenesis by the carboxyl terminus of angiopoietin-like protein 4. Arterioscler Thromb Vasc Biol. 2008;28:835-40 pubmed publisher
    ..The carboxyl terminus of Angptl4 alone is sufficient to suppress angiogenesis, possibly through inhibiting the Raf/MEK/ERK1/2 MAP kinase pathway in endothelial cells.
  22. Salama R, Muramatsu H, Zou P, Okayama M, Muramatsu T. Midkine, a heparin-binding growth factor, produced by the host enhances metastasis of Lewis lung carcinoma cells. Cancer Lett. 2006;233:16-20 pubmed
    b>Midkine is a heparin-binding growth factor and is expressed by a number of tumor cells, contributing to their growth both in vitro and in vivo...
  23. Molinsky J, Klanova M, Maswabi B, Soukup T, Trneny M, Necas E, et al. In vivo growth of mantle cell lymphoma xenografts in immunodeficient mice is positively regulated by VEGF and associated with significant up-regulation of CD31/PECAM1. Folia Biol (Praha). 2013;59:26-31 pubmed
    ..The most downregulated genes in both JEKO-1 and HBL-2 xenografts were midkine (MDK) and ephrine B2 (EPHB2)...
  24. Sato W, Takei Y, Yuzawa Y, Matsuo S, Kadomatsu K, Muramatsu T. Midkine antisense oligodeoxyribonucleotide inhibits renal damage induced by ischemic reperfusion. Kidney Int. 2005;67:1330-9 pubmed
    b>Midkine, a heparin-binding growth factor, is involved in the migration of inflammatory cells...
  25. Kim Y, Ryu J, Lee H, Lim I, Park D, Lee M, et al. Midkine, heparin-binding growth factor, blocks kainic acid-induced seizure and neuronal cell death in mouse hippocampus. BMC Neurosci. 2010;11:42 pubmed publisher
    b>Midkine (MK), a member of the heparin-binding growth factor family, which includes MK and pleiotrophin, is known to possess neurotrophic and neuroprotective properties in the central nervous system...
  26. Chen H, He D, Lasek A. Midkine in the mouse ventral tegmental area limits ethanol intake and Ccl2 gene expression. Genes Brain Behav. 2017;16:699-708 pubmed publisher
    b>Midkine (MDK) is a cytokine and neurotrophic factor that is more highly expressed in the brains of alcoholics and in mice predisposed to drink large amounts of ethanol, suggesting that MDK may regulate ethanol consumption...
  27. Vicente Rodríguez M, Perez Garcia C, Haro M, Ramos M, Herradon G. Genetic inactivation of midkine modulates behavioural responses to ethanol possibly by enhancing GABA(A) receptor sensitivity to GABA(A) acting drugs. Behav Brain Res. 2014;274:258-63 pubmed publisher
    b>Midkine (MK) is a cytokine with important functions in dopaminergic neurons that is found upregulated in the prefrontal cortex of alcoholics...
  28. Gramage E, Perez Garcia C, Vicente Rodríguez M, Bollen S, Rojo L, Herradon G. Regulation of extinction of cocaine-induced place preference by midkine is related to a differential phosphorylation of peroxiredoxin 6 in dorsal striatum. Behav Brain Res. 2013;253:223-31 pubmed publisher
    The neurotrophic factors Midkine (MK) and Pleiotrophin (PTN) have been suggested to modulate drugs of abuse-induced effects...
  29. Kishida S, Kadomatsu K. Involvement of midkine in neuroblastoma tumourigenesis. Br J Pharmacol. 2014;171:896-904 pubmed publisher
    b>Midkine is highly expressed in various cancers, including neuroblastoma, one of the most malignant paediatric solid tumours known...
  30. Eickhoff H, Schuchhardt J, Ivanov I, Meier Ewert S, O Brien J, Malik A, et al. Tissue gene expression analysis using arrayed normalized cDNA libraries. Genome Res. 2000;10:1230-40 pubmed
    ..The obtained results are publicly available ( and can be used by other researchers as a digital expression reference. ..
  31. Peichel C, Scherer S, Tsui L, Beier D, Vogt T. Mapping the midkine family of developmentally regulated signaling molecules. Mamm Genome. 1993;4:632-8 pubmed
    b>Midkine (Mdk) and heparin-binding neurotrophic factor (Hbnf)/pleiotrophin (Ptn) comprise the Midkine family of developmentally regulated signaling molecules...
  32. Matsubara S, Tomomura M, Kadomatsu K, Muramatsu T. Structure of a retinoic acid-responsive gene, MK, which is transiently activated during the differentiation of embryonal carcinoma cells and the mid-gestation period of mouse embryogenesis. J Biol Chem. 1990;265:9441-3 pubmed
    ..Then, there was a sequence common to all MK cDNAs consisting of four exons. The results indicate that different species of MK mRNA are generated by the use of alternative promoters and different modes of splicing. ..
  33. Suzuki N, Shibata Y, Urano T, Murohara T, Muramatsu T, Kadomatsu K. Proteasomal degradation of the nuclear targeting growth factor midkine. J Biol Chem. 2004;279:17785-91 pubmed
    ..Degradation of endocytosed midkine, a heparin-binding growth factor, was suppressed by both proteasome and lysosome inhibitors to similar extents...
  34. Prediger R, Rojas Mayorquín A, Aguiar A, Chevarin C, Mongeau R, Hamon M, et al. Mice with genetic deletion of the heparin-binding growth factor midkine exhibit early preclinical features of Parkinson's disease. J Neural Transm (Vienna). 2011;118:1215-25 pubmed publisher
    ..b>Midkine is a 13-kDa retinoic acid-induced heparin-binding growth factor involved in many biological processes in the ..
  35. Wallin J, Mizutani Y, Imai K, Miyashita N, Moriwaki K, Taniguchi M, et al. A new Pax gene, Pax-9, maps to mouse chromosome 12. Mamm Genome. 1993;4:354-8 pubmed
  36. Dreger R, Harris M, Peichel C, Vogt T, Juriloff D. The first arch (Far) mutation in mice recombines with Hoxd and Mdk. Mamm Genome. 1995;6:662-3 pubmed
  37. Qiu L, Hyink D, Gans W, Amsler K, Wilson P, Burrow C. Midkine promotes selective expansion of the nephrogenic mesenchyme during kidney organogenesis. Organogenesis. 2004;1:14-21 pubmed
    ..b>Midkine, a target gene activated by retinoid signaling in the metanephros, encodes a secreted polypeptide with mitogenic ..
  38. Chu F, Naiditch J, Clark S, Qiu Y, Zheng X, Lautz T, et al. Midkine Mediates Intercellular Crosstalk between Drug-Resistant and Drug-Sensitive Neuroblastoma Cells In Vitro and In Vivo. ISRN Oncol. 2013;2013:518637 pubmed publisher
    ..Previous work identified midkine (MK) as a novel putative survival molecule responsible for cytoprotective signaling between drug-resistant and ..
  39. Ikutomo M, Sakakima H, Matsuda F, Yoshida Y. Midkine-deficient mice delayed degeneration and regeneration after skeletal muscle injury. Acta Histochem. 2014;116:319-26 pubmed publisher
    b>Midkine (MK), a heparin-binding growth factor, was previously found to be expressed in the rat myotube-forming stage...
  40. Yao X, Tan Z, Gu B, Wu R, Liu Y, Dai L, et al. Promotion of self-renewal of embryonic stem cells by midkine. Acta Pharmacol Sin. 2010;31:629-37 pubmed publisher
    To characterize the expression and function of midkine (MK) in an in vitro embryonic stem cell (ESC) culture system. To investigate the potential roles of MK, the expression of MK in ESCs was evaluated by RT-PCR and immunocytochemistry...
  41. Kaplan F, Comber J, Sladek R, Hudson T, Muglia L, Macrae T, et al. The growth factor midkine is modulated by both glucocorticoid and retinoid in fetal lung development. Am J Respir Cell Mol Biol. 2003;28:33-41 pubmed
    ..cDNA microarray analysis showed organ-specific upregulation of the retinoic acid responsive gene midkine (MK) and its chondroitin-sulfate binding partner PG-M/versican at fetal day 18 and at neonatal day 1 in lungs of ..
  42. Singh P, Srivastava V. Recombinant expression and purification of heparin binding proteins: midkine and pleiotrophin from Escherichia coli. Protein Expr Purif. 2012;85:181-6 pubmed publisher
    b>Midkine (MDK) and Pleiotrophin (PTN) belong to a class of heparin-binding growth factors and are highly expressed in a number of cancers. Bioactive and recombinant MDK and PTN are critical reagent for cancer drug discovery studies...
  43. Inoh K, Muramatsu H, Ochiai K, Torii S, Muramatsu T. Midkine, a heparin-binding cytokine, plays key roles in intraperitoneal adhesions. Biochem Biophys Res Commun. 2004;317:108-13 pubmed
    b>Midkine is a heparin-binding cytokine or growth factor and promotes the migration of inflammatory leukocytes. Upon partial hepatectomy, adhesion of the intestine was less severe in midkine-deficient mice than in wild-type mice...
  44. Horiba M, Kadomatsu K, Yasui K, Lee J, Takenaka H, Sumida A, et al. Midkine plays a protective role against cardiac ischemia/reperfusion injury through a reduction of apoptotic reaction. Circulation. 2006;114:1713-20 pubmed
    b>Midkine (MK) is a heparin-binding growth factor involved in diverse biological phenomena, eg, neural survival, carcinogenesis, and tissue repair...
  45. Park Y, Franklin J, Settle S, Levy S, Chung E, Jeyakumar L, et al. Gene expression profile analysis of mouse colon embryonic development. Genesis. 2005;41:1-12 pubmed
  46. Kawai H, Sato W, Yuzawa Y, Kosugi T, Matsuo S, Takei Y, et al. Lack of the growth factor midkine enhances survival against cisplatin-induced renal damage. Am J Pathol. 2004;165:1603-12 pubmed
    ..The growth factor midkine is highly expressed in the proximal tubule and exerts ambivalent activities as to cisplatin nephrotoxicity, ie, ..
  47. Mitsiadis T, Caton J, De Bari C, Bluteau G. The large functional spectrum of the heparin-binding cytokines MK and HB-GAM in continuously growing organs: the rodent incisor as a model. Dev Biol. 2008;320:256-66 pubmed publisher
    ..These results demonstrate that MK and HB-GAM are involved in stem cells maintenance, cytodifferentiation and mineralization processes during mouse incisor development. ..
  48. Inoue S, Moriya M, Watanabe Y, Miyagawa Tomita S, Niihori T, Oba D, et al. New BRAF knockin mice provide a pathogenetic mechanism of developmental defects and a therapeutic approach in cardio-facio-cutaneous syndrome. Hum Mol Genet. 2014;23:6553-66 pubmed publisher
    ..Prenatal treatment with a MEK inhibitor, PD0325901, rescued the embryonic lethality with amelioration of craniofacial abnormalities and edema in ..
  49. Sato Y, Sato W, Maruyama S, Wilcox C, Falck J, Masuda T, et al. Midkine Regulates BP through Cytochrome P450-Derived Eicosanoids. J Am Soc Nephrol. 2015;26:1806-15 pubmed publisher
    ..We previously reported that the endothelial growth factor midkine (MK) enhances hypertension in a model of CKD...
  50. Peichel C, Abbott C, Vogt T. Genetic and physical mapping of the mouse Ulnaless locus. Genetics. 1996;144:1757-67 pubmed
    ..Therefore, the region that must contain the Ulnaless locus has been defined and cloned, which will be invaluable for the identification of the molecular nature of the Ulnaless mutation. ..
  51. Ohgake S, Shimizu E, Hashimoto K, Okamura N, Koike K, Koizumi H, et al. Dopaminergic hypofunctions and prepulse inhibition deficits in mice lacking midkine. Prog Neuropsychopharmacol Biol Psychiatry. 2009;33:541-6 pubmed publisher
    b>Midkine is a 13-kDa retinoic acid-induced heparin-binding growth factor involved in various biological phenomena such as cell migration, neurogenesis, and tissue repair...
  52. Lener M, Fernandes M, Poirier C, Bazzali Hernandez C, Tosi M, Meo T. The C1 inhibitor encoding gene (C1nh) maps to mouse chromosome 2. Mamm Genome. 1998;9:94 pubmed
  53. Kim I, Ramakrishna S, Gusarova G, Yoder H, Costa R, Kalinichenko V. The forkhead box m1 transcription factor is essential for embryonic development of pulmonary vasculature. J Biol Chem. 2005;280:22278-86 pubmed
    ..In summary, development of mouse lungs depends on the Foxm1 transcription factor, which regulates expression of genes essential for mesenchyme proliferation, extracellular matrix remodeling, and vasculogenesis. ..
  54. Weckbach L, Gola A, Winkelmann M, Jakob S, Groesser L, Borgolte J, et al. The cytokine midkine supports neutrophil trafficking during acute inflammation by promoting adhesion via ?2 integrins (CD11/CD18). Blood. 2014;123:1887-96 pubmed publisher
    Emerging evidence suggests a role of the cytokine midkine (MK) in inflammation. In this study, its functional relevance for recruitment of polymorphonuclear neutrophils (PMNs) during acute inflammation was investigated...
  55. Jochheim Richter A, Rüdrich U, Koczan D, Hillemann T, Tewes S, Petry M, et al. Gene expression analysis identifies novel genes participating in early murine liver development and adult liver regeneration. Differentiation. 2006;74:167-73 pubmed
    ..homeodomain transcription factor 2 (Pitx2) were exclusively detected at 24 hr, whereas the genes Twist1, Midkine, and zinc finger protein of cerebellum 1 (Zic1) each showed a specific expression profile in the regenerating ..
  56. Latham K, Sapienza C. Localization of genes encoding egg modifiers of paternal genome function to mouse chromosomes one and two. Development. 1998;125:929-35 pubmed
    ..These data demonstrate clearly that differences in how the egg cytoplasm modifies the incoming paternal genome are indeed genetically determined, and vary accordingly. ..
  57. Simon Chazottes D, Matsubara S, Miyauchi T, Muramatsu T, Guenet J. Chromosomal localization of two cell surface-associated molecules of potential importance in development: midkine (Mdk) and basigin (Bsg). Mamm Genome. 1992;2:269-71 pubmed
  58. Tsutsui J, Uehara K, Kadomatsu K, Matsubara S, Muramatsu T. A new family of heparin-binding factors: strong conservation of midkine (MK) sequences between the human and the mouse. Biochem Biophys Res Commun. 1991;176:792-7 pubmed
    A retinoic acid responsive gene, MK, specifies for a heparin binding factor termed midkine (MK), which is the initial member of a new protein family involved in regulation of growth and differentiation...
  59. Fan N, Sun H, Wang Y, Zhang L, Xia Z, Peng L, et al. Midkine, a potential link between obesity and insulin resistance. PLoS ONE. 2014;9:e88299 pubmed publisher
    ..b>Midkine (MK) is a heparin-binding growth factor with potent proinflammatory activities...
  60. Ingram D, Hiatt K, King A, Fisher L, Shivakumar R, Derstine C, et al. Hyperactivation of p21(ras) and the hematopoietic-specific Rho GTPase, Rac2, cooperate to alter the proliferation of neurofibromin-deficient mast cells in vivo and in vitro. J Exp Med. 2001;194:57-69 pubmed
    ..Rac2 functions as mediator of cross-talk between phosphoinositide 3-kinase (PI-3K) and the classical p21(ras)-Raf-Mek-ERK pathway to confer a distinct proliferative advantage to Nf1(+/)- mast cells...
  61. Kaneda N, Talukder A, Nishiyama H, Koizumi S, Muramatsu T. Midkine, a heparin-binding growth/differentiation factor, exhibits nerve cell adhesion and guidance activity for neurite outgrowth in vitro. J Biochem. 1996;119:1150-6 pubmed
    By means of a baculovirus expression system, a large amount of mouse midkine (MK) was produced. The protein was purified to homogeneity by heparin-Sepharose column chromatography...
  62. Sato W, Kadomatsu K, Yuzawa Y, Muramatsu H, Hotta N, Matsuo S, et al. Midkine is involved in neutrophil infiltration into the tubulointerstitium in ischemic renal injury. J Immunol. 2001;167:3463-9 pubmed
    b>Midkine (MK) is a multifunctional heparin-binding protein and promotes migration of neutrophils, macrophages, and neurons. In the normal mouse kidney, MK is expressed in the proximal tubules...
  63. Matsuura O, Kadomatsu K, Takei Y, Uchimura K, Mimura S, Watanabe K, et al. Midkine expression is associated with postnatal development of the lungs. Cell Struct Funct. 2002;27:109-15 pubmed
    A heparin-binding growth factor, midkine, is the product of a retinoic acid-responsive gene...
  64. Gramage E, Martin Y, Ramanah P, Perez Garcia C, Herradon G. Midkine regulates amphetamine-induced astrocytosis in striatum but has no effects on amphetamine-induced striatal dopaminergic denervation and addictive effects: functional differences between pleiotrophin and midkine. Neuroscience. 2011;190:307-17 pubmed publisher
    b>Midkine (MK), a neurotrophic factor with important roles in survival and differentiation of dopaminergic neurons, is upregulated in different brain areas after administration of different drugs of abuse suggesting MK could modulate drugs ..
  65. Liedert A, Mattausch L, Röntgen V, Blakytny R, Vogele D, Pahl M, et al. Midkine-deficiency increases the anabolic response of cortical bone to mechanical loading. Bone. 2011;48:945-51 pubmed publisher
    ..Based on a recent study, which has shown that the deficiency of growth factor midkine (Mdk) in mice at 12 and 18 months of age resulted in increased trabecular bone formation, we hypothesized that ..
  66. Naito A, Yoshikura H, Iwamoto A. Similarity of the genomic structure between the two members in a new family of heparin-binding factors. Biochem Biophys Res Commun. 1992;183:701-7 pubmed
    ..Although the exon organization was similar to that of midkine, another member of the same family of heparin-binding factors, the sizes of introns were much larger and occupied ..
  67. Kosugi T, Yuzawa Y, Sato W, Kawai H, Matsuo S, Takei Y, et al. Growth factor midkine is involved in the pathogenesis of diabetic nephropathy. Am J Pathol. 2006;168:9-19 pubmed
    ..Using the Streptozotocin-induced model of diabetes, we report that mice deficient in the growth factor midkine (Mdk-/-) exhibited strikingly milder nephropathy than Mdk+/+ mice, even though both mice showed similar extents ..
  68. Gramage E, Herradon G, Martin Y, Vicente Rodríguez M, Rojo L, Gnekow H, et al. Differential phosphoproteome of the striatum from pleiotrophin knockout and midkine knockout mice treated with amphetamine: correlations with amphetamine-induced neurotoxicity. Toxicology. 2013;306:147-56 pubmed publisher
    The neurotrophic factors pleiotrophin (PTN) and midkine (MK) have been shown to modulate amphetamine-induced neurotoxicity. Accordingly, PTN-/- and MK-/- mice show an increased vulnerability to amphetamine-induced neurotoxic effects...
  69. Koseki H, Zachgo J, Mizutani Y, Simon Chazottes D, Guenet J, Balling R, et al. Fine genetic mapping of the proximal part of mouse chromosome 2 excludes Pax-8 as a candidate gene for Danforth's short tail (Sd). Mamm Genome. 1993;4:324-7 pubmed
    ..part of Chromosome (Chr) 2, three genes qualified as possible candidates: Pax-8, a paired box-containing gene; Midkine (Mdk), a retinoic acid-responsive gene; and a new locus (Etl-4) identified by enhancer trapping with a lacZ ..
  70. Zou P, Muramatsu H, Sone M, Hayashi H, Nakashima T, Muramatsu T. Mice doubly deficient in the midkine and pleiotrophin genes exhibit deficits in the expression of beta-tectorin gene and in auditory response. Lab Invest. 2006;86:645-53 pubmed
    ..b>Midkine and pleiotrophin are closely related proteins that serve as growth factors and cytokines...
  71. Haffner Luntzer M, Heilmann A, Rapp A, Beie S, Schinke T, Amling M, et al. Midkine-deficiency delays chondrogenesis during the early phase of fracture healing in mice. PLoS ONE. 2014;9:e116282 pubmed publisher
    The growth and differentiation factor midkine (Mdk) plays an important role in bone development and remodeling. Mdk-deficient mice display a high bone mass phenotype when aged 12 and 18 months...
  72. Nakamura E, Kadomatsu K, Yuasa S, Muramatsu H, Mamiya T, Nabeshima T, et al. Disruption of the midkine gene (Mdk) resulted in altered expression of a calcium binding protein in the hippocampus of infant mice and their abnormal behaviour. Genes Cells. 1998;3:811-22 pubmed
    b>Midkine (MK) is a growth factor implicated in the development and repair of various tissues, especially neural tissues. However, its in vivo function has not been clarified...
  73. Hao H, Maeda Y, Fukazawa T, Yamatsuji T, Takaoka M, Bao X, et al. Inhibition of the growth factor MDK/midkine by a novel small molecule compound to treat non-small cell lung cancer. PLoS ONE. 2013;8:e71093 pubmed publisher
    b>Midkine (MDK) is a heparin-binding growth factor that is highly expressed in many malignant tumors, including lung cancers. MDK activates the PI3K pathway and induces anti-apoptotic activity, in turn enhancing the survival of tumors...
  74. Ito K, Yanagida A, Okada K, Yamazaki Y, Nakauchi H, Kamiya A. Mesenchymal progenitor cells in mouse foetal liver regulate differentiation and proliferation of hepatoblasts. Liver Int. 2014;34:1378-90 pubmed publisher
    ..Foetal mesenchymal cells expressed pleiotrophin, hepatocyte growth factor and midkine 1, which are involved in the growth of hepatoblasts...
  75. Diamond Stanic M, Romero Aleshire M, Hoyer P, Greer K, Hoying J, Brooks H. Midkine, a heparin-binding protein, is increased in the diabetic mouse kidney postmenopause. Am J Physiol Renal Physiol. 2011;300:F139-46 pubmed publisher
    ..We randomly selected genes for confirmation by real-time PCR; midkine (Mdk), immediate early response gene 3 (IEX-1), mitogen-inducible gene 6 (Mig6), and ubiquitin-specific protease ..
  76. Shibata Y, Muramatsu T, Hirai M, Inui T, Kimura T, Saito H, et al. Nuclear targeting by the growth factor midkine. Mol Cell Biol. 2002;22:6788-96 pubmed
    ..We recently showed that LRP binds heparin-binding growth factor midkine. Here we demonstrate that LRP mediates nuclear targeting by midkine and that the nuclear targeting is ..
  77. Reynolds P, Mucenski M, Whitsett J. Thyroid transcription factor (TTF) -1 regulates the expression of midkine (MK) during lung morphogenesis. Dev Dyn. 2003;227:227-37 pubmed
    b>Midkine (MK) is a 13-kDa heparin-binding growth factor that is thought to mediate developmental processes, including vasculogenesis, cell migration, and proliferation in various organs...
  78. Brunet de Carvalho N, Raulais D, Rauvala H, Souttou B, Vigny M. HB-GAM/Pleiotrophin and Midkine are differently expressed and distributed during retinoic acid-induced neural differentiation of P19 cells. Growth Factors. 2003;21:139-49 pubmed
    HB-GAM/Pleiotrophin and Midkine (MK) are developmentally-regulated proteins with putative functions during cell growth and differentiation...
  79. Winkler C, Yao S. The midkine family of growth factors: diverse roles in nervous system formation and maintenance. Br J Pharmacol. 2014;171:905-12 pubmed publisher
    ..During postnatal stages, midkine expression generally ceases but is often up-regulated under disease conditions, most notably those affecting the ..
  80. Paxson J, Gruntman A, Davis A, Parkin C, Ingenito E, Hoffman A. Age dependence of lung mesenchymal stromal cell dynamics following pneumonectomy. Stem Cells Dev. 2013;22:3214-25 pubmed publisher
    ..and Pdgfr?, and up-regulation of mRNA encoding Fap, Eln, Col1a1, Col3a1, Aldh1a3, Arhgef25, Dner, Fgfr1, and Midkine. However, compared with LMSCs isolated from young mice, LMSCs from older mice exhibited reduced mRNA expression ..
  81. Mitsiadis T, Salmivirta M, Muramatsu T, Muramatsu H, Rauvala H, Lehtonen E, et al. Expression of the heparin-binding cytokines, midkine (MK) and HB-GAM (pleiotrophin) is associated with epithelial-mesenchymal interactions during fetal development and organogenesis. Development. 1995;121:37-51 pubmed
    b>Midkine (MK) and heparin binding-growth associated molecule (HB-GAM or pleiotrophin), constitute a new family of heparin-binding proteins implicated in the regulation of growth and differentiation (T. Muramatsu (1993) Int. J. Dev. Biol...
  82. Chan P, Simon Chazottes D, Mattei M, Guenet J, Salier J. Comparative mapping of lipocalin genes in human and mouse: the four genes for complement C8 gamma chain, prostaglandin-D-synthase, oncogene-24p3, and progestagen-associated endometrial protein map to HSA9 and MMU2. Genomics. 1994;23:145-50 pubmed
    ..By in situ hybridization, the human LCN2 gene maps to HSA9q34. Our data indicate that the lipocalin locus arrangement in the human/mouse ancestor is closer to that found at HSA9q than to that in the MMU genome. ..
  83. Muramatsu H, Zou P, Kurosawa N, Ichihara Tanaka K, Maruyama K, Inoh K, et al. Female infertility in mice deficient in midkine and pleiotrophin, which form a distinct family of growth factors. Genes Cells. 2006;11:1405-17 pubmed
    b>Midkine and pleiotrophin form a family of growth factors. Mice deficient in one of the genes show few abnormalities on reproduction and development...
  84. Kadomatsu K, Huang R, Suganuma T, Murata F, Muramatsu T. A retinoic acid responsive gene MK found in the teratocarcinoma system is expressed in spatially and temporally controlled manner during mouse embryogenesis. J Cell Biol. 1990;110:607-16 pubmed
    ..These data suggest that MK gene plays a fundamental role in the differentiation of a wide variety of cells; MK gene may also play some specific roles in generation of epithelial tissues, and remodeling of mesoderm. ..
  85. Kadomatsu K. [Mechanisms of action of the growth factor midkine]. Tanpakushitsu Kakusan Koso. 2008;53:1619-24 pubmed
  86. Adachi Y, Matsubara S, Pedraza C, Ozawa M, Tsutsui J, Takamatsu H, et al. Midkine as a novel target gene for the Wilms' tumor suppressor gene (WT1). Oncogene. 1996;13:2197-203 pubmed
    b>Midkine (MK) is a heparin-binding growth factor which is strongly expressed during the midgestation period of mouse embryogenesis...