Prevention and Treatment of Experimental Glomerulonephritis Using Recombinant Uteroglobin.
- Author:
Seung Hee YANG
1
;
You Young KIM
;
Hyun Joo CHUNG
;
Hyun Lee KIM
;
Sang Gu LEE
;
Sei Han LEE
;
Sung Kyun KIM
;
Nam Hyun CHUNG
;
Yon Su KIM
Author Information
1. Seoul National University Hospital Clinical Research Institute, Korea.
- Publication Type:Original Article
- Keywords:
Anti-GBM glomerulonephritis;
Uteroglobin;
prevention
- MeSH:
Animals;
Basement Membrane;
Glomerulonephritis*;
Humans;
Hypersensitivity;
Injections, Intravenous;
Mice;
Models, Theoretical;
Proteinuria;
Uteroglobin*
- From:Korean Journal of Nephrology
2002;21(4):560-568
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
Glomerulonephritis(GN) is characterized by cognate immune responses against self or non-self antigen. It is suggested that the crescentic GN is a manifestation of cell-mediated immune response akin to delayed type hypersensitivity. Uteroglobin(UG) is a steroid-dependent, immunomodulatory, and cytokine-like protein. It was reported that UG prevented fibronectin(Fn) deposition in the glomeruli of normal mice to form Fn-UG heterodimers that competed with Fn self-aggregation. We hypothesized that UG would prevent the development of experimental GN induced by anti-glomerular basement membrane globulin(anti-GBM Ab) in mice through immunomodulatory properties. GN was induced by intravenous injection of 4.5 mg rabbit anti-GBM Ab to mice(C57BL/6). Renal injury was evaluated at 7, 14, and 21 days thereafter. UG-treated mice(n=10) were received for 3 days(0.5 mg/mouse/day) beginning 1 hour after anti-GBM Ab injection. Also, disease-control mice(n=10) were received PBS for 3 days after anti-GBM Ab. Proteinuria was significantly reduced in the mice treated with UG when compared with the disease-control mice after 7 and 14 days of anti-GBM Ab injection. The amount of proteinuria was similar between UG treated and normal control mice. The mesangial matrix expansion and cellular crescent were markedly attenuated by the injection of UG. The proliferative responses of mesangial cells(C57BL/6) to LPS were blunted with the addition of UG in dose-dependent manner. In this study, we revealed the preventive effects of UG in the experimental model of glomerulonephritis. This result in turn could provide the basis for the treatment of human disease such as chronic glomerulonephritis.
