Neutralization of macrophage-stimulating protein ameliorates renal injury in anti-thy 1 glomerulonephritis.

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.

• Authors: Teresa Rampino, Grazia Soccio, Marilena Gregorini, Cristina Guidetti, Maddalena Marasà, Milena Maggio, Vincenzo Panichi, Massimiliano Migliori, Carmelo Libetta, Antonio Dal Canton
• Journal: Journal of the American Society of Nephrology : JASN (J Am Soc Nephrol) Vol. 18 Issue 5 Pg. 1486-96 (May 2007) ISSN: 1046-6673 [Print] United States
• PMID: 17409315 (Publication Type: Journal Article)

Chemical References

• Actins
• Antibodies
• Complement C3
• Isoantibodies
• Proliferating Cell Nuclear Antigen
• Proto-Oncogene Proteins
• anti-Thy antibody
• macrophage stimulating protein
• smooth muscle actin, rat
• Hepatocyte Growth Factor
• Creatinine
• RON protein
• Receptor Protein-Tyrosine Kinases

Topics

• Actins (metabolism)
• Animals
• Antibodies (pharmacology)
• Cell Movement
• Complement C3 (immunology)
• Creatinine (blood)
• Female
• Glomerulonephritis (etiology, pathology)
• Hepatocyte Growth Factor (antagonists & inhibitors, blood, immunology, urine)
• Isoantibodies
• Kidney (drug effects, metabolism, physiopathology)
• Monocytes (cytology, metabolism)
• Proliferating Cell Nuclear Antigen (metabolism)
• Proteinuria (chemically induced)
• Proto-Oncogene Proteins (antagonists & inhibitors, blood, immunology, urine)
• Rats
• Rats, Wistar
• Receptor Protein-Tyrosine Kinases (metabolism)