title: Growth factor Midkine is involved in the pathogenesis of renal injury induced by protein overload containing endotoxin.
abstract: BACKGROUND
  Growth factor Midkine (MK), which expresses on endothelial cells and renal proximal tubules, has been implicated in inflammation-related kidney diseases such as ischemic reperfusion-induced tubulointerstitial injury and diabetic nephropathy. The biological actions of MK are elicited through its chemotactic activity and chemokine-driven inflammatory pathway. Post-infectious glomerulonephritis is caused by the deposition of immune complexes into glomeruli by infiltrating a number of inflammatory cells. Therefore, we investigated whether MK might be involved in the pathogenesis of acute glomerulonephritis.
  
  
  METHODS
  We induced endocapillary proliferative glomerulonephritis in 129/SV mice using intraperitoneal injections of a large amount of protein.
  
  
  RESULTS
  In contrast to mice deficient in MK (Mdk (-/-)), Mdk (+/+) mice induced by protein overload demonstrated more diffuse cellular proliferation in the mesangial areas and capillary lumens, eventually leading to glomerular damage and tubulointerstitial injury. This pathological observation could be attributable to neutrophil infiltration through the chemotaxis and stimulation of the MK-macrophage inflammatory protein (MIP)-2 pathway, but appeared to be due to the MK-related immunoglobulin (Ig)G deposition and C3 activation. These findings are often seen in infectious-related glomerular injury. Furthermore, the profile of MK expression was strongly consistent with that of glomerular damage and tubulointersititial injury.
  
  
  CONCLUSIONS
  This study might provide a new insight into understanding the deleterious role of MK in endocapillary proliferative glomerulonephritis induced by protein overload.
authors.affiliation: Division of Nephrology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, Aichi, 466-8550, Japan.
authors.forename: Kiyonari
authors.initials: K
authors.lastname: Kato
authors.affiliation: Division of Nephrology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, Aichi, 466-8550, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Kosugi
authors.affiliation: Division of Nephrology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, Aichi, 466-8550, Japan. waichi@med.nagoya-u.ac.jp.
authors.forename: Waichi
authors.initials: W
authors.lastname: Sato
authors.affiliation: Division of Nephrology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, Aichi, 466-8550, Japan.
authors.forename: Hanayo
authors.initials: H
authors.lastname: Arata-Kawai
authors.affiliation: Division of Nephrology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, Aichi, 466-8550, Japan.
authors.forename: Takenori
authors.initials: T
authors.lastname: Ozaki
authors.affiliation: Division of Nephrology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, Aichi, 466-8550, Japan.
authors.forename: Naotake
authors.initials: N
authors.lastname: Tsuboi
authors.affiliation: Division of Nephrology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, Aichi, 466-8550, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Ito
authors.affiliation: Tawada Clinic, 2-15-23 Kaminagoya Nishi-ku, Nagoya, Aichi, 451-0025, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Tawada
authors.affiliation: Division of Nephrology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, Aichi, 466-8550, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Yuzawa
authors.affiliation: Division of Nephrology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, Aichi, 466-8550, Japan.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Matsuo
authors.affiliation: Division of Biochemistry, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, Aichi, 466-8550, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kadomatsu
authors.affiliation: Division of Nephrology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, Aichi, 466-8550, Japan.
authors.forename: Shoichi
authors.initials: S
authors.lastname: Maruyama
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000096:biosynthesis; D054426:Chemokine CXCL2 / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis / Q000502:physiology*; D005260:Female; D005921:Glomerulonephritis / Q000139:chemically induced* / Q000473:pathology; D007074:Immunoglobulin G / Q000378:metabolism; D007678:Kidney Glomerulus / Q000473:pathology; D051379:Mice; D008854:Microscopy, Electron; D000078792:Midkine; D011507:Proteinuria / Q000209:etiology; D012710:Serum Albumin, Bovine / Q000009:adverse effects; D016212:Transforming Growth Factor beta / Q000096:biosynthesis
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D054426:Chemokine CXCL2; C404915:Cxcl2 protein, mouse; D016207:Cytokines; D007074:Immunoglobulin G; D016212:Transforming Growth Factor beta; D000078792:Midkine; D012710:Serum Albumin, Bovine