Disease relevance of Mdk

• Daily administration of ATRA ameliorated proteinuria, which was accompanied by the improvement in the effacement of the foot processes and by the induction of nephrin and midkine [1].
• On day 5 of PAN nephrosis, RALDH2 showed the remarkable induction, whereas glomerular expression levels of nephrin and midkine, one of the ATRA target genes, were downregulated [1].
• Monoclonal antibody to human midkine reveals increased midkine expression in human brain tumors [2].
• The values of the PCNA-labeling index were statistically higher in GBMs, medulloblastomas, PNETs, Br-Mts, and L-Mts that expressed MK than in those that did not (Wilcoxon rank-sum test, p < 0.05) [2].
• MK protein was detected immunohistochemically in 58.3% of alveolar hyperplasias, 92.3% of adenomas and 100% of adenocarcinomas and squamous cell carcinomas [3].

Psychiatry related information on Mdk

• It was reported that MK was present in senile plaques of Alzheimer's disease (AD) [4].

High impact information on Mdk

• The HB-GAM sequence clearly (about 50%) is homologous to that of MK (midkine) sequence, a protein discovered through screening for factors that mediate retinoic acid-induced cell differentiation [5].
• Human ryudocan from endothelium-like cells binds basic fibroblast growth factor, midkine, and tissue factor pathway inhibitor [6].
• Midkine (MK) is a retinoic acid responsive gene for a heparin-binding growth factor [7].
• On day 16, MK is expressed in the condensed mesenchyme and in early epithelialized mesenchymal derivatives [7].
• In metanephroi explanted from 14-d-old fetuses and cultured in a defined medium, expression of MK mRNA was found to be stimulated when retinoic acid (100 nM) was added in the culture medium [7].

Chemical compound and disease context of Mdk

• To evaluate the protective effects of midkine (MK), the product of a retinoic acid-responsive gene, on constant light-induced retinal degeneration in albino Sprague-Dawley rats [8].
• To investigate whether MK plays a role in breast cancer, we examined MK mRNA expression in N-nitroso-N-methylurea-induced rat mammary tumors at various stages of tumor progression, including hormone independence and distant metastasis [9].
• Myocardial infarction induces expression of midkine, a heparin-binding growth factor with reparative activity [10].
• Pertussis toxin and benzalkonium chloride inhibited the histamine release induced by midkine [11].

Biological context of Mdk

• We conclude that Mdk is involved early in fetal development of the rat adrenal [12].
• The remaining neuroepithelial cells, with the exception of those in M-phase and the tips of processes at the ventricular surface, were negative for MK immunohistochemistry 16-24 hr after the administration of ENU [13].
• Finally, in vitro nephrogenesis was strongly inhibited in the presence of neutralizing antibodies for MK: the number of nephrons formed in vitro was reduced by approximately 50% without changes in ureteric bud branching morphogenesis [7].
• Following the ischemia, up-regulation of MK mRNA and a corresponding increase of its protein products were found in the hippocampal CA1 subfield [14].
• Midkine and RPTP-beta gene expression in rat stomach was investigated by laser capture microdissection coupled with the reverse transcription-polymerase chain reaction (RT-PCR) [15].

Anatomical context of Mdk

• In normal rat fetuses, MK immunostaining was observed in the cytoplasm and radial and horizontal processes of all cells in the neuroepithelium (NE), subventricular zone (SV), and intermediate zone (IMZ) [13].
• Intense MK immunoreactivity was detected in the ipsilateral spinal motor neurons of the anterior horn of the lumbar spinal cord after 1 day and in ipsilateral and contralateral spinal motor neurons from 4 days to 1 week after injury [16].
• Midkine expression in rat spinal motor neurons following sciatic nerve injury [16].
• However, the role of MK in peripheral nerve injury has not been clarified [16].
• In situ hybridization showed the expression of MK mRNA in lumbar spinal motor neurons of the anterior horn, but it was not present in Schwann cells or non-neuronal cells [16].

Associations of Mdk with chemical compounds

• MK is a heparin-binding growth factor that occurs as a product of a retinoic acid-inducible gene, and has a molecular mass of 13 kDa [13].
• In utero exposure to vitamin A deficiency did not modify the specific spatial and temporal expression pattern of MK gene in the metanephros, although a decrease in mRNA expression occurred [7].
• Overexpression of midkine in lung tumors induced by N-nitrosobis(2-hydroxypropyl)amine in rats and its increase with progression [3].
• Rebamipide stimulated both midkine and RPTP-beta expression in rat stomach and RGM1 cells [15].
• Midkine in the progression of rat N-nitroso-N-methylurea-induced mammary tumors [9].

Regulatory relationships of Mdk

• Midkine inhibits apoptosis via extracellular signal regulated kinase (ERK) activation in PC12 cells [17].

Other interactions of Mdk

• Transglutaminase-mediated amine incorporation, midkine and isopeptide cross-links were co-localized to axonal adhesion sites [18].
• Localization of pleiotrophin and midkine in the postnatal developing cerebellum [19].

Analytical, diagnostic and therapeutic context of Mdk

• MK expression was examined immunohistochemically and by immunoelectron microscopy during a period of repair in developing rat brain at the neurogenesis stage [13].
• The aim of the present study was therefore to quantify the expression of MK mRNA during renal development in the rat, to analyze the regulation of MK expression by retinoids in vivo and in vitro, and, finally, to study the role of MK in rat metanephric organ cultures [7].
• MK mRNA expression of adenocarcinomas and squamous cell carcinomas assessed by means of the reverse transcriptase-polymerase chain reaction and northern blot analysis was significantly higher than in rat embryonic tissues (positive controls) and contrasted strongly with the lack in normal lungs [3].
• The expression of MK was examined up to 14 days after the injury by immunohistochemical and Western blot analyses [20].
• The effects of rebamipide on midkine and RPTP-beta expression in rat stomach and the gastric epithelial cell line RGM1 were evaluated by RT-PCR and Northern blot analyses [15].

References