Midkine is involved in tubulointerstitial inflammation associated with diabetic nephropathy

Kosugi, Tomoki; Yuzawa, Yukio; Sato, Waichi; Arata-Kawai, Hanayo; Suzuki, Norihiko; Kato, Noritoshi; Matsuo, Seiichi; Kadomatsu, Kenji

doi:10.1038/labinvest.3700599

Cited by 76 publications

(80 citation statements)

References 32 publications

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“…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). The mechanisms mentioned above may also operate in the involvement of midkine in the pathogenesis of UC since the accumulation of neutrophiles and monocytes associated with aberrant inflammatory response is essential for development of UC (14).…”

Section: Discussionmentioning

confidence: 99%

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: Discussionmentioning

confidence: 99%

Clinical relevance of circulating midkine in ulcerative colitis

Krzystek−Korpacka

Neubauer

Matusiewicz

2009

Clinical Chemistry and Laboratory Medicine

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“…38 Briefly, the renal cortex divided from the medulla was resolved with collagenase (Wako Chemicals, Miyazaki, Japan) and the lysate was then filtered through 38-m strainer, using a mesh sieving method. The fluid was centrifuged to pellet the various renal cells, which were plated with cultured media for 1 hour of incubation.…”

Section: Cell Culturementioning

confidence: 99%

Basigin/CD147 Promotes Renal Fibrosis after Unilateral Ureteral Obstruction

Kato

Kosugi

Sato

et al. 2011

The American Journal of Pathology

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Regardless of their primary causes, progressive renal fibrosis and tubular atrophy are the main predictors of progression to end-stage renal disease. Basigin/ CD147 is a multifunctional molecule-it induces matrix metalloproteinases and hyaluronan, for example-and has been implicated in organ fibrosis. However, the relationship between basigin and organ fibrosis has been poorly studied. We investigated basigin's role in renal fibrosis using a unilateral ureteral obstruction model. Basigin-deficient mice (Bsg ؊/؊ ) demonstrated significantly less fibrosis after surgery than Bsg ؉/؉ mice. Fewer macrophages had infiltrated in Bsg ؊/؊ kidneys. Consistent with these in vivo data, primary cultured tubular epithelial cells from Bsg ؊/؊ mice produced less matrix metalloproteinase and exhibited less motility on stimulation with transforming growth factor ␤. Furthermore, Bsg ؊/؊ embryonic fibro blasts produced less hyaluronan and ␣-smooth muscle actin after transforming growth factor ␤ stimulation. Together, these results demonstrate for the first time that basigin is a key regulator of renal fibrosis. Basigin could be a candidate target molecule for the prevention of organ fibrosis.

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“…144 In a mouse model of IRI, it was found that MK levels were increased threefold in proximal tubular cells, leading to neutrophil recruitment and resulting in an inflammatory reaction and tubulointerstitial damage. 143 It was believed that superoxide anions produced during the IRI procedure led to the upregulation of MK, and it is feasible that MK expression could be altered during CI-AKI.…”

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confidence: 99%

The potential use of biomarkers in predicting contrast-induced acute kidney injury

Andreucci¹,

Faga²,

Riccio³

et al. 2016

IJNRD

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Contrast-induced acute kidney injury (CI-AKI) is a problem associated with the use of iodinated contrast media, causing kidney dysfunction in patients with preexisting renal failure. It accounts for 12% of all hospital-acquired kidney failure and increases the length of hospitalization, a situation that is worsening with increasing numbers of patients with comorbidities, including those requiring cardiovascular interventional procedures. So far, its diagnosis has relied upon the rise in creatinine levels, which is a late marker of kidney damage and is believed to be inadequate. Therefore, there is an urgent need for biomarkers that can detect CI-AKI sooner and more reliably. In recent years, many new biomarkers have been characterized for AKI, and these are discussed particularly with their use in known CI-AKI models and studies and include neutrophil gelatinase-associated lipocalin, cystatin C (Cys-C), kidney injury molecule-1, interleukin-18, N-acetyl-β-d-glucosaminidase, and L-type fatty acid-binding protein (L-FABP). The potential of miRNA and metabolomic technology is also mentioned. Early detection of CI-AKI may lead to early intervention and therefore improve patient outcome, and in future any one or a combination of several of these markers together with development in technology for their analysis may prove effective in this respect.

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Midkine is involved in tubulointerstitial inflammation associated with diabetic nephropathy

Cited by 76 publications

References 32 publications

Clinical relevance of circulating midkine in ulcerative colitis

Clinical relevance of circulating midkine in ulcerative colitis

Basigin/CD147 Promotes Renal Fibrosis after Unilateral Ureteral Obstruction

The potential use of biomarkers in predicting contrast-induced acute kidney injury

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