Attributes of antiangiogenic factor plasminogen kringle 5 in glomerulonephritis.
BACKGROUND
Plasminogen kringle domain (K) 5 is known to inhibit endothelial cell growth, but limited data are available investigating the relationship between K5 and glomerulonephritis (GN).


OBJECTIVE
To understand the relationships among K5, GN, and glomerular endothelial cells in GN mice models and human subjects.


METHODS
Two mice models of GN and 2 categories of human GN biopsy samples were collected to gain insight into the disease mechanism from the laboratory to bedside. In the mechanistic animal study, membranous nephropathy (MN) and focal segmental glomerulosclerosis mice models were used. Kringle domain 5 in the diseased kidney was located by immunofluorescence and quantified by Western blotting. In the kinetic animal study, different MN time points were stained with K5, immunoglobulin G, and C3 by immunofluorescence. CD31 and proliferating cell nuclear antigen were evaluated by immunohistochemical double staining for alterations in the glomerular endothelial cells. Biopsy samples from patients diagnosed with antibody (Ab)-mediated and non-Ab-mediated GN were collected for K5 analysis.


RESULTS
The expression level of K5 was found to be significant in MN, but not in focal segmental glomerulosclerosis, and was markedly elevated in the diseased glomeruli along the capillary walls. Kringle domain 5 levels increased steadily with the evolution of MN, appearing after the deposition of Abs. In altered glomerular endothelial cells, CD31 decreased with the evolution of MN. In human subjects, K5 occurred only in patients with Ab GN.


CONCLUSIONS
Kringle domain 5 might be involved in the progression of Ab-mediated GN and associated with the alteration of MN glomerular endothelial cell growth.
Department of Internal Medicine, Tri-Service General Hospital, Taipei, Taiwan. dgschen@ndmctsgh.edu.tw
Jin-Shuen
JS
Chen
Jyh-Chang
JC
Hwang
Li-Chien
LC
Chang
Chia-Chao
CC
Wu
Yuh-Feng
YF
Lin
D020533:Angiogenesis Inhibitors / Q000378:metabolism*; D000818:Animals; D001706:Biopsy; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D015433:Glomerulonephritis, Membranous / Q000378:metabolism* / Q000473:pathology; D005923:Glomerulosclerosis, Focal Segmental / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007678:Kidney Glomerulus / Q000098:blood supply / Q000648:ultrastructure; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000378:metabolism*; D010958:Plasminogen / Q000378:metabolism*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D010446:Peptide Fragments; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D018809:Proliferating Cell Nuclear Antigen; C491499:plasminogen kringle 5; D010958:Plasminogen