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Neutralization of macrophage-stimulating protein ameliorates renal injury in anti-thy 1 glomerulonephritis.
- Source :
-
Journal of the American Society of Nephrology : JASN [J Am Soc Nephrol] 2007 May; Vol. 18 (5), pp. 1486-96. Date of Electronic Publication: 2007 Apr 04. - Publication Year :
- 2007
-
Abstract
- Macrophage-stimulating protein (MSP) is a scatter factor that causes cell proliferation and migration, and receptor origin nantaise (RON) is its receptor. RON is expressed in macrophages and mesangial cells, and MSP is produced by renal tubular cells. This study investigated whether MSP/RON participate in the pathogenesis of anti-Thy 1 nephritis, a glomerular disease that is characterized by invasion of circulating monocytes into glomeruli and migration and proliferation of mesangial cells. In vivo, renal function and histopathology were studied in rats that had anti-Thy 1 disease and were untreated and treated with a neutralizing anti-MSP antibody. In vitro, whether monocytes express RON and whether MSP has a chemotactic effect on monocytes were studied. In vivo, in anti-Thy 1 disease, MSP was expressed de novo in glomeruli, and neutralization of MSP attenuated the rise in serum creatinine and proteinuria, stopped glomerular neutrophil and monocyte influx, protected from glomerular injury, and lessened mesangial cell overgrowth. In vitro, unstimulated monocytes did not express RON, but the stimulation with LPS induced de novo RON expression. LPS-stimulated monocytes were attracted by MSP. These results demonstrate a pathogenic role of the MSP/RON system in anti-Thy 1 nephritis.
- Subjects :
- Actins metabolism
Animals
Antibodies pharmacology
Cell Movement
Complement C3 immunology
Creatinine blood
Female
Glomerulonephritis etiology
Hepatocyte Growth Factor blood
Hepatocyte Growth Factor urine
Kidney drug effects
Kidney metabolism
Monocytes cytology
Monocytes metabolism
Proliferating Cell Nuclear Antigen metabolism
Proteinuria chemically induced
Proto-Oncogene Proteins blood
Proto-Oncogene Proteins urine
Rats
Rats, Wistar
Receptor Protein-Tyrosine Kinases metabolism
Glomerulonephritis pathology
Hepatocyte Growth Factor antagonists & inhibitors
Hepatocyte Growth Factor immunology
Isoantibodies
Kidney physiopathology
Proto-Oncogene Proteins antagonists & inhibitors
Proto-Oncogene Proteins immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1046-6673
- Volume :
- 18
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of the American Society of Nephrology : JASN
- Publication Type :
- Academic Journal
- Accession number :
- 17409315
- Full Text :
- https://doi.org/10.1681/ASN.2006060680