Midkine, a heparin-binding cytokine with multiple roles in development, repair and diseases

Midkine is a heparin-binding cytokine or a growth factor with a molecular weight of 13 kDa. Midkine binds to oversulfated structures in heparan sulfate and chondroitin sulfate. The midkine receptor is a molecular complex containing proteoglycans. Midkine promotes migration, survival and other activities of target cells. Midkine has about 50% sequence identity with pleiotrophin. Mice deficient in both factors exhibit severe abnormalities including female infertility. In adults, midkine is expressed in damaged tissues and involved in the reparative process. It is also involved in inflammatory reactions by promoting the migration of leukocytes, induction of chemokines and suppression of regulatory T cells. Midkine is expressed in a variety of malignant tumors and promotes their growth and invasion. Midkine appears to be helpful for the treatment of injuries in the heart, brain, spinal cord and retina. Midkine inhibitors are expected to be effective in the treatment of malignancies, rheumatoid arthritis, multiple sclerosis, renal diseases, restenosis, hypertension and adhesion after surgery.

• Publication year

  2010

• Venue

  Proceedings of the Japan Academy. Series B, Physical and biological sciences

• Publication date

  2010-04-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.2183/pjab.86.410PMID 20431264PMCID 3417803
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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• Disruption of the midkine gene (Mdk) delays degeneration and regeneration in injured peripheral nerve

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• In vitro and in vivo suppression of hepatocellular carcinoma growth by midkine-antisense oligonucleotide-loaded nanoparticles.

  2009cited by this paper
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  2009cited by this paper
• Midkine prevents ventricular remodeling and improves long-term survival after myocardial infarction.

  2009cited by this paper
• The growth factor midkine regulates the renin-angiotensin system in mice.

  2009cited by this paper
• Midkine induces epithelial-mesenchymal transition through Notch2/Jak2-Stat3 signaling in human keratinocytes

  2008cited by this paper
• Impact of alcohol abuse on protein expression of midkine and excitatory amino acid transporter 1 in the human prefrontal cortex.

  2008cited by this paper
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  2008cited by this paper
• Glycosaminoglycan‐binding cytokines as tumor markers

  2008cited by this paper
• Inhibition of midkine alleviates experimental autoimmune encephalomyelitis through the expansion of regulatory T cell population

  2008cited by this paper
• Plasma midkine level is a prognostic factor for human neuroblastoma

  2008cited by this paper
• Midkine Enhances Soft-Tissue Sarcoma Growth: A Possible Novel Therapeutic Target

  2008cited by this paper
• Midkine‐b regulates cell specification at the neural plate border in zebrafish

  2008cited by this paper
• Midkine and its clinical significance in endometrial carcinoma

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• Midkine accumulated in nucleolus of HepG2 cells involved in rRNA transcription.

  2008cited by this paper
• Therapeutic effect of midkine on cardiac remodeling in infarcted rat hearts.

  2008cited by this paper
• Morphine and yohimbine regulate midkine gene expression in the rat hippocampus.

  2007cited by this paper
• Clinical significance of midkine expression in pancreatic head carcinoma

  2007cited by this paper
• Midkine is an autocrine activator of signal transducer and activator of transcription 3 in 3T3-L1 cells.

  2007cited by this paper
• Increased midkine gene expression in childhood B-precursor acute lymphoblastic leukemia.

  2007cited by this paper
• Recruitment of insulin receptor substrate-1 and activation of NF-κB essential for midkine growth signaling through anaplastic lymphoma kinase

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• Gene Expression Profiling Reveals Potential Biomarkers of Human Hepatocellular Carcinoma

  2007cited by this paper
• Therapeutic effect of midkine on cardiac remodeling in infarcted rat hearts

  2007cited by this paper
• Overexpression of midkine contributes to anti‐apoptotic effects in human meningiomas

  2007cited by this paper
• Midkine as a novel target for antibody therapy in osteosarcoma.

  2007cited by this paper
• Evaluation of expression of midkine in oral squamous cell carcinoma and its correlation with tumour angiogenesis.

  2007cited by this paper
• Midkine and LDL-receptor-related protein 1 contribute to the anchorage-independent cell growth of cancer cells

  2007cited by this paper
• Midkine, a heparin‐binding growth factor, is expressed in neural precursor cells and promotes their growth

  2006cited by this paper
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  2006cited by this paper
• Midkine as a molecular target: comparison of effects of chondroitin sulfate E and siRNA.

  2006cited by this paper
• Midkine Plays a Protective Role Against Cardiac Ischemia/Reperfusion Injury Through a Reduction of Apoptotic Reaction

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• Midkine is a potent regulator of the catecholamine biosynthesis pathway in mouse aorta.

  2006cited by this paper
• Serum levels of midkine, a heparin-binding growth factor, increase in both malignant and benign gynecological tumors

  2006cited by this paper
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• Female infertility in mice deficient in midkine and pleiotrophin, which form a distinct family of growth factors

  2006cited by this paper
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  2006cited by this paper
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  2006cited by this paper
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  2006cited by this paper
• Neuroglycan C Is a Novel Midkine Receptor Involved in Process Elongation of Oligodendroglial Precursor-like Cells*

  2006cited by this paper
• Growth factor midkine is involved in the pathogenesis of diabetic nephropathy.

  2006cited by this paper
• Increased midkine levels in sera from patients with Alzheimer's disease.

  2005cited by this paper
• Miple1 and miple2 encode a family of MK/PTN homologues in Drosophila melanogaster

  2005cited by this paper
• Medial floor plate formation in zebrafish consists of two phases and requires trunk-derived Midkine-a.

  2005cited by this paper
• Truncated midkine induces transformation of cultured cells and short latency of tumorigenesis in nude mice.

  2005cited by this paper
• Possible implication of midkine in the development of endometriosis.

  2005cited by this paper
• 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.

  2005cited by this paper
• Characterization of Heparin Affin Regulatory Peptide Signaling in Human Endothelial Cells*

  2005cited by this paper
• Midkine antisense oligodeoxyribonucleotide inhibits renal damage induced by ischemic reperfusion.

  2005cited by this paper
• Identification of midkine as a mediator for intercellular transfer of drug resistance

  2005cited by this paper
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  2005cited by this paper
• Postischemic gene transfer of midkine, a neurotrophic factor, protects against focal brain ischemia

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• Midkine protects hepatocellular carcinoma cells against TRAIL-mediated apoptosis through down-regulation of caspase-3 activity

  2004cited by this paper
• Chromosomal localization of two cell surface-associated molecules of potential importance in development: Midkine (Mdk) and basigin (Bsg)

  2004cited by this paper
• Midkine protects hepatocellular carcinoma cells against TRAIL‐mediated apoptosis through down‐regulation of caspase‐3 activity

  2004cited by this paper
• Midkine and pleiotrophin in neural development and cancer.

  2004cited by this paper
• alpha4beta1- and alpha6beta1-integrins are functional receptors for midkine, a heparin-binding growth factor.

  2004cited by this paper
• Correlation of elevated level of blood midkine with poor prognostic factors of human neuroblastomas

  2004cited by this paper
• The role of midkine and pleiotrophin in liver regeneration

  2004cited by this paper
• α4β1- and α6β1-integrins are functional receptors for midkine, a heparin-binding growth factor

  2004cited by this paper
• Midkine, a heparin-binding growth factor, is fundamentally involved in the pathogenesis of rheumatoid arthritis.

  2004cited by this paper
• Midkine, a heparin-binding cytokine, plays key roles in intraperitoneal adhesions.

  2004cited by this paper
• Midkine Promoter Can Mediate Transcriptional Activation of a Fused Suicide Gene in a Broader Range of Human Breast Cancer Compared with c-erbB-2 Promoter

  2004cited by this paper
• Identification of Genes with Differential Expression in Acquired Drug-Resistant Gastric Cancer Cells Using High-Density Oligonucleotide Microarrays

  2004cited by this paper
• Lack of the growth factor midkine enhances survival against cisplatin-induced renal damage.

  2004cited by this paper
• Midkine Is Regulated by Hypoxia and Causes Pulmonary Vascular Remodeling*

  2004cited by this paper
• Glycosaminoglycan structures required for strong binding to midkine, a heparin-binding growth factor.

  2003cited by this paper
• Correlation of elevated level of blood midkine with poor prognostic factors of human neuroblastomas

  2003cited by this paper
• Preoperative serum midkine concentration is a prognostic marker for esophageal squamous cell carcinoma

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• A promoter region of the midkine gene that is frequently expressed in human hepatocellular carcinoma can activate a suicide gene as effectively as the α-fetoprotein promoter

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• Production of native recombinant human midkine in the yeast, Pichia pastoris.

  2003cited by this paper
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  2003cited by this paper
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• Recognition of glycosaminoglycans by midkine.

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  2002cited by this paper
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• Nuclear Targeting by the Growth Factor Midkine

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  2001cited by this paper
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• Midkine Is Involved in Neutrophil Infiltration into the Tubulointerstitium in Ischemic Renal Injury1

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• Antisense oligodeoxynucleotide targeted to Midkine, a heparin-binding growth factor, suppresses tumorigenicity of mouse rectal carcinoma cells.

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• Midkine binds to 37-kDa laminin binding protein precursor, leading to nuclear transport of the complex.

  2001cited by this paper
• Haptotactic Migration Induced by Midkine

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• Intraventricular administration of the neurotrophic factor midkine ameliorates hippocampal delayed neuronal death following transient forebrain ischemia in gerbils.

  2001cited by this paper
• Detection of truncated midkine in Wilms' tumor by a monoclonal antibody against human recombinant truncated midkine.

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• Inhibition of HIV infection by the cytokine midkine.

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• Protein-bound carbohydrates on cell-surface as targets of recognition: An Odyssey in understanding them

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• Neuronal Cell Adhesion, Mediated by the Heparin-binding Neuroregulatory Factor Midkine, Is Specifically Inhibited by Chondroitin Sulfate E

  2000cited by this paper
• Midkine promoter-based adenoviral vector gene delivery for pediatric solid tumors.

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• Inhibition of Aβ fibril formation and Aβ-induced cytotoxicity by senile plaque-associated proteins

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• Midkine enhances early stages of collagen gel contraction.

  2000cited by this paper
• Neointima formation in a restenosis model is suppressed in midkine-deficient mice.

  2000cited by this paper
• Serum midkine levels are increased in patients with various types of carcinomas

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  2018cites this paper
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  2018cites this paper
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  2018cites this paper
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