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. Conclusion: This study might provide a new insight into understanding the deleterious role of MK in endocapillary proliferative glomerulonephritis induced by protein overload.
| Original language | English |
|---|---|
| Pages (from-to) | 346-354 |
| Number of pages | 9 |
| Journal | Clinical and Experimental Nephrology |
| Volume | 15 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 01-06-2011 |
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All Science Journal Classification (ASJC) codes
- Physiology
- Nephrology
- Physiology (medical)
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Growth factor Midkine is involved in the pathogenesis of renal injury induced by protein overload containing endotoxin. / Kato, Kiyonari; Kosugi, Tomoki; Sato, Waichi; Arata-Kawai, Hanayo; Ozaki, Takenori; Tsuboi, Naotake; Ito, Isao; Tawada, Hideo; Yuzawa, Yukio; Matsuo, Seiichi; Kadomatsu, Kenji; Maruyama, Shoichi.
In: Clinical and Experimental Nephrology, Vol. 15, No. 3, 01.06.2011, p. 346-354.Research output: Contribution to journal › Article
TY - JOUR
T1 - Growth factor Midkine is involved in the pathogenesis of renal injury induced by protein overload containing endotoxin
AU - Kato, Kiyonari
AU - Kosugi, Tomoki
AU - Sato, Waichi
AU - Arata-Kawai, Hanayo
AU - Ozaki, Takenori
AU - Tsuboi, Naotake
AU - Ito, Isao
AU - Tawada, Hideo
AU - Yuzawa, Yukio
AU - Matsuo, Seiichi
AU - Kadomatsu, Kenji
AU - Maruyama, Shoichi
PY - 2011/6/1
Y1 - 2011/6/1
N2 - 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. Conclusion: This study might provide a new insight into understanding the deleterious role of MK in endocapillary proliferative glomerulonephritis induced by protein overload.
AB - 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. Conclusion: This study might provide a new insight into understanding the deleterious role of MK in endocapillary proliferative glomerulonephritis induced by protein overload.
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UR - http://www.scopus.com/inward/citedby.url?scp=79959198691&partnerID=8YFLogxK
U2 - 10.1007/s10157-011-0408-2
DO - 10.1007/s10157-011-0408-2
M3 - Article
C2 - 21360016
AN - SCOPUS:79959198691
VL - 15
SP - 346
EP - 354
JO - Clinical and Experimental Nephrology
JF - Clinical and Experimental Nephrology
SN - 1342-1751
IS - 3
ER -