Recombinant uteroglobin prevents the experimental crescentic glomerulonephritis.
BACKGROUND
Although uteroglobin is known to have an immunomodulatory property and prevents the deposition of immune-complexes on the glomeruli of mice, the therapeutic potential of uteroglobin is uncertain in glomerulonephritis. To test the hypothesis that uteroglobin can prevent glomerulonephritis, we have studied the effects of recombinant uteroglobin on the development of experimental crescentic glomerulonephritis that is induced by anti-glomerular basement membrane (anti-GBM) antibodies.


RESULTS
Glomerulonephritis was induced by the intravenous injection of rabbit anti-GBM globulin antibodies into mice (C57BL/6), and renal injury was evaluated 7, 14, and 21 days afterward. Recombinant uteroglobin or phosphate-buffered saline (PBS) were given intravenously to mice for 3 days after anti-GBM antibody injection. Proteinuria was significantly reduced in mice treated with recombinant uteroglobin compared with disease-control mice at 7 and 14 days after an anti-GBM antibody injection, although the serum creatinine concentration was similar in both groups. The amount of proteinuria was similar in recombinant uteroglobin-treated and normal control mice. By histologic analysis, mesangial matrix expansion, mesangial proliferation, and cellular crescents representing crescentic glomerulonephritis were markedly attenuated by injection of recombinant uteroglobin. The in vitro proliferative responses of mesangial cells to lipopolysaccharide (LPS) were blunted by the addition of recombinant uteroglobin in a dose-dependent manner. The preventive effects exerted by recombinant uteroglobin treatment were based on the inhibition of antibodies and complement-3 deposition on the glomeruli.


CONCLUSIONS
This study demonstrates the preventive effects of recombinant uteroglobin in an experimental model of crescentic glomerulonephritis, and suggests the therapeutic implications of uteroglobin for human chronic glomerulonephritis.
Cancer Research Institute, Department of Anatomy, Seoul National University College of Medicine, Seoul, Korea.
Dong-Sup
DS
Lee
Seung Hee
SH
Yang
Hyun Lee
HL
Kim
Kwon Wook
KW
Joo
Chun Soo
CS
Lim
Dong-Wan
DW
Chae
Suhnggwon
S
Kim
Jung Sang
JS
Lee
Yon Su
YS
Kim
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001323:Autoantibodies; D045744:Cell Line, Tumor; D005260:Female; D005920:Glomerular Mesangium / Q000187:drug effects / Q000473:pathology; D005921:Glomerulonephritis / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008175:Lung Neoplasms; D051379:Mice; D008810:Mice, Inbred C57BL; D011507:Proteinuria / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control; D011817:Rabbits; D011994:Recombinant Proteins / Q000494:pharmacology; D014598:Uteroglobin / Q000494:pharmacology*
D000906:Antibodies; D001323:Autoantibodies; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; C051951:antiglomerular basement membrane antibody; D014598:Uteroglobin