Midkine, a Retinoic Acid-Inducible Heparin-Binding Cytokine in Inflammatory Responses: Chemotactic Activity to Neutrophils and Association with Inflammatory Synovitis

Takada, Tohru; Toriyama, Kazuhiro; Muramatsu, Hisako; Xia, Song; Torii, Shuhei; Muramatsu, Takashi

doi:10.1093/oxfordjournals.jbchem.a021773

Cited by 143 publications

(130 citation statements)

References 45 publications

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“…Our results are in agreement with postulated involvement of midkine in the perpetuation and exacerbation of the inflammatory response (5,6). It may play a role in recruitment of neutrophils and macrophages into inflamed tissue (23,24), and up-regulation of synthesis of inflammatory mediators (25)(26)(27). Animal studies have revealed that several inflammation-related phenomena were substantially alleviated in midkine-deficient animals (12,25,(28)(29)(30)(31)(32).…”

Section: Discussionsupporting

confidence: 89%

Clinical relevance of circulating midkine in ulcerative colitis

Krzystek−Korpacka

Neubauer

Matusiewicz

2009

Clinical Chemistry and Laboratory Medicine

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Background: Non-invasive biochemical markers are needed to support the diagnosis of ulcerative colitis (UC), an incurable disease of unknown pathology. Midkine is an angiogenic cytokine, chemotactic towards neutrophils and macrophages, and a T-regulatory cell suppressor. Methods: Serum midkine was measured immunoenzymatically in 93 UC patients and 108 healthy subjects, and evaluated with respect to disease status, endoscopic, inflammatory and angiogenic activity. The diagnostic value of midkine was compared to Creactive protein (CRP) using receiver operating characteristics (ROC) analysis. Results: Midkine was higher (p-0.0001) in inactive (199 ng/L) and active UC (351 ng/L) compared with controls (93 ng/L), and reflected disease activity (rs0.427, p-0.001). Midkine was correlated with CRP, erythrocyte sedimentation rate (ESR), leukocytes, platelets, interleukin-6, paraoxonase-1, albumin, transferrin, iron, hemoglobin, and hematocrit. Midkine correlated with angiogenic factors: vascular endothelial growth factor-A and platelet-derived growth factor-BB. As a marker of UC, midkine showed a diagnostic accuracy of 85%, sensitivity of 72%, specificity of 82%, whereas CRP showed 83%, 65% and 91%, respectively. As a marker of active UC, midkine showed a diagnostic accuracy of 87%, sensitivity of 84%, specificity of 75%, whereas CRP showed 75%, 63% and 83%, respectively. Combined assessment of midkine and CRP improved sensitivity but substantially decreased specificity. Conclusions: UC is associated with increased circulating midkine, which corresponds with clinical, endoscopic, inflammatory and angiogenic activity, and anemia. Performance of midkine as a marker of UC or active UC was comparable to that of CRP. Clin Chem Lab Med 2009;47:1085-90.

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Section: Discussionsupporting

confidence: 89%

Clinical relevance of circulating midkine in ulcerative colitis

Krzystek−Korpacka

Neubauer

Matusiewicz

2009

Clinical Chemistry and Laboratory Medicine

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“…17 In this model, the inflammatory cells are again key players. Consistent with the in vitro chemotactic activity of MK, 20,21 inflammatory cell recruitment is significantly suppressed in MdkϪ/Ϫ mice in both models. 17,21 Another important activity of MK is an anti-apoptotic one.…”

supporting

confidence: 79%

“…Although it is known that MK has chemotactic activity to neutrophils and macrophages, 20,21 there are no reports for T cells. No matter how MK exhibits effects on chemotaxis of macrophages and T cells, differences of infiltration of these cells between Mdkϩ/ϩ and MdkϪ/Ϫ mice became apparent in later time points, when MK expression is lower than the normal level in Mdkϩ/ϩ mice.…”

Section: Discussionmentioning

confidence: 99%

Lack of the Growth Factor Midkine Enhances Survival against Cisplatin-Induced Renal Damage

Kawai

Sato

Yuzawa

et al. 2004

The American Journal of Pathology

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Although cisplatin acts directly on proximal tubule epithelial cells and causes cell death, little is known regarding the biological significance of its secondary effects, such as inflammation. The growth factor midkine is highly expressed in the proximal tubule and exerts ambivalent activities as to cisplatin nephrotoxicity, ie, anti-apoptotic and chemotactic ones. Here we report that midkine-deficient mice show a significantly higher survival rate than wild-type mice. The levels of blood urea nitrogen and tubular degeneration and apoptosis were higher in wild-type mice despite the anti-apoptotic activity of midkine. We found that recruitment of neutrophils was more enhanced in wild-type mice, this being consistent with the chemotactic activity of midkine. Midkine expression in wild-type mice persisted for 24 hours, and then dramatically decreased. Preadministration of midkine anti-sense oligodeoxyribonucleotide to wildtype mice suppressed midkine expression, and consequently neutrophil infiltration. It is of note that neutrophil infiltration, apoptosis, and elevation of blood urea nitrogen became conspicuous sequentially, namely 1, 2, and 3 days after cisplatin administration, respectively. These findings suggest that early molecular events involving midkine induce inflammatory response and their circuits eventually enhance the death of the proximal tubule epithelial cells. The results indicate the crucial role of inflammation in cisplatin-induced renal damage, and provide a candidate molecular target for its prevention. Cisplatin [cis-dichlorodiammine-platinum (II), CDDP] is widely used to treat carcinoma patients. However, its full clinical utility is significantly limited because of its nephrotoxicity. The main site of CDDP action is in proximal tubule epithelial cells. In proliferating cancer cells, CDDP inhibits DNA and RNA synthesis. In contrast, the effects of CDDP on nonproliferating cells, such as proximal tubule epithelial cells, can be categorized into mainly two primary types.

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“…Its expression is induced as early as at the precancerous stages of human colorectal and prostate carcinomas (Konishi et al, 1999;Ye et al, 1999), increases with the stages of human carcinomas, and is significantly linked to the prognosis (O'Brien et al, 1996;Mishima et al, 1997). MK transforms NIH3T3 cells , enhances fibrinolysis (Kojima et al, 1995), and promotes cell growth (Muramatsu and Muramatsu, 1991;Muramatsu et al, 1993;Takei et al, 2001), cell survival (Qi et al, 2000), cell migration (Takada et al, 1997;Maeda et al, 1999;Horiba et al, 2000;Qi et al, 2001), and angiogenesis (Choudhuri et al, 1997). MK antisense oligodeoxyribonucleotide suppresses tumour progression in nude mice (Takei et al, 2001(Takei et al, , 2002.…”

mentioning

confidence: 99%

Correlation of elevated level of blood midkine with poor prognostic factors of human neuroblastomas

et al. 2003

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The heparin-binding growth factor midkine (MK) is the product of a retinoic acid-responsive gene, and is implicated in neuronal survival and differentiation, and carcinogenesis. We previously reported that MK mRNA expression is elevated in neuroblastoma specimens at all stages, whereas pleiotrophin, the other member of the MK family, is expressed at high levels in favourable neuroblastomas. As MK is a secretory protein, it can be detected in the blood. Here, we show a significant correlation of the plasma MK level with prognostic factors of neuroblastomas. The plasma MK level was determined in 220 patients with neuroblastomas, and compared with that in children without malignant tumors (n ¼ 17, o500 pg ml À1 ). The plasma MK level became significantly elevated with advancing stages (stage 1: 445 pg ml À1 (median), n ¼ 73; stage 2: 589, n ¼ 39; stage 3: 864, n ¼ 40; stage 4: 1445, n ¼ 56; and stage 4S: 2439, n ¼ 12). More importantly, a higher MK level was strongly correlated with poor prognostic factors: over 1 year of age (P ¼ 0.0299), MYCN amplification (Po0.0001), low TrkA expression (P ¼ 0.0005), nonmass screening, sporadic neuroblastomas (Po0.0001), and diploidy/tetraploidy (P ¼ 0.0007). Thus, these results demonstrate that the plasma MK level is a good marker for evaluating the progression of neuroblastomas. Moreover, considering the ability of antisense MK oligodeoxyribonucleotide to suppress tumour growth of colorectal carcinoma cells in nude mice, as recently reported, the present study suggests that MK is a possible candidate molecular target for therapy for neuroblastomas.

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Midkine, a Retinoic Acid-Inducible Heparin-Binding Cytokine in Inflammatory Responses: Chemotactic Activity to Neutrophils and Association with Inflammatory Synovitis

Cited by 143 publications

References 45 publications

Clinical relevance of circulating midkine in ulcerative colitis

Clinical relevance of circulating midkine in ulcerative colitis

Lack of the Growth Factor Midkine Enhances Survival against Cisplatin-Induced Renal Damage

Correlation of elevated level of blood midkine with poor prognostic factors of human neuroblastomas

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