The protective role of uteroglobin through the modulation of tissue transglutaminase in the experimental crescentic glomerulonephritis.
METHODS
Tissue transglutaminase (tTG) may induce pro-inflammatory cytokines and produce irreversible end-products, thus promoting renal scarring. It has recently been confirmed that the crescent formation in murine experimental crescentic glomerulonephritis (ecGN) has been inhibited by the administration of recombinant uteroglobin (rUG). However, the ability of UG on tTG modulation has not been thoroughly assessed. In this study, we investigated the feasible protective role of UG in murine ecGN through the modulation of tTG and TGF-beta1 expressions. ecGN was induced by the administration of anti-GBM Ab into C57BL/6 mice.


RESULTS
Both proteinuria and BUN levels were distinctively lower in rUG-treated mice compared to those of disease control mice. Glomerular injuries such as mesangial proliferation, matrix production and crescent formation were lessened with the rUG treatment, and these findings were parallel with the attenuated expression of tTG and TGF-beta1. tTG and TGF-beta1 were expressed mainly on mesangial areas by the induction of ecGN and rUG treatment markedly attenuated the expressions of these proteins in glomeruli without spatial changes. With the addition of LPS to mesangial cells, the expressions of tTG and TGF-beta1 were up-regulated, whilst the addition of cysteamine, tTG inhibitor, attenuated the expression of tTG and TGF-beta1 as well as the cellular proliferation which was further induced by LPS.


CONCLUSIONS
We demonstrate for the first time that rUG is able to attenuate the renal injury through the modulation of expressions of tTG and TGF-beta1 in ecGN and further suggest a wide range of feasible molecular targets to reduce the severity of human glomerulonephritis.
Yang
Seung Hee
SH
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, 110-744, Korea.
Shin
Sung Joon
SJ
Oh
Ji Eun
JE
Jin
Ji Zhe
JZ
Chung
Nam Hyun
NH
Lim
Chun Soo
CS
Kim
Suhnggwon
S
Kim
Yon Su
YS
D000818:Animals; D000888:Antibodies, Anti-Idiotypic; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005921:Glomerulonephritis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D050527:Mesangial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000494:pharmacology; D012720:Severity of Illness Index; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D011503:Transglutaminases / Q000378:metabolism*; D014598:Uteroglobin / Q000494:pharmacology*
D000888:Antibodies, Anti-Idiotypic; D011994:Recombinant Proteins; D053773:Transforming Growth Factor beta1; D014598:Uteroglobin; D011503:Transglutaminases