کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5937470 | 1573408 | 2013 | 10 صفحه PDF | دانلود رایگان |
Inflammatory cell infiltration and fibrin deposition play important roles in the development of crescentic glomerulonephritis (GN). In particular, activation of coagulation is an indispensable factor in crescent formation. However, the mechanisms underlying the pathogenesis of crescent formation have not been completely elucidated. We identified the growth factor midkine (MK) as a novel key molecule in the progression of crescentic GN induced by anti-glomerular basement membrane antibody. Despite the lack of significant differences in autologous and heterologous reactions, MK-deficient (Mdkâ/â) mice unexpectedly showed a greater number of necrotizing glomerular injuries than wild-type (Mdk+/+) mice. Likewise, more tubulointerstitial damage was observed in Mdkâ/â mice, and this damage positively correlated with glomerular injury. Plasminogen activator inhibitor (PAI)-1 was strongly induced in the injured glomerulus of Mdkâ/â mice, particularly in crescents and endothelial cells. This enhanced PAI-1 production was associated with an increase in inflammatory cell infiltration and matrix deposition in the glomerulus and the interstitium of Mdkâ/â mice. In line with these in vivo data, primary cultured endothelial cells derived from Mdkâ/â mice exhibited higher PAI-1 mRNA expression on fibrin challenge and less fibrinolysis than Mdk+/+ mice. In contrast, the expression of plasminogen activators was not affected. Our combined data suggest that MK leads to a blockade of PAI-1, which is closely associated with the suppression of crescentic GN.
Journal: The American Journal of Pathology - Volume 182, Issue 2, February 2013, Pages 410-419