Neutralization of macrophage-stimulating protein ameliorates renal injury in anti-thy 1 glomerulonephritis.
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.
Rampino
Teresa
T
Unit of Nephrology, Dialysis and Transplantation, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo and University of Pavia, Pavia, Italy. t.rampino@smatteo.pv.it
Soccio
Grazia
G
Gregorini
Marilena
M
Guidetti
Cristina
C
Marasà
Maddalena
M
Maggio
Milena
M
Panichi
Vincenzo
V
Migliori
Massimiliano
M
Libetta
Carmelo
C
Dal Canton
Antonio
A
D000199:Actins / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002465:Cell Movement; D003176:Complement C3 / Q000276:immunology; D003404:Creatinine / Q000097:blood; D005260:Female; D005921:Glomerulonephritis / Q000209:etiology / Q000473:pathology*; D017228:Hepatocyte Growth Factor / Q000037:antagonists & inhibitors* / Q000097:blood / Q000276:immunology* / Q000652:urine; D007518:Isoantibodies; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011507:Proteinuria / Q000139:chemically induced; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000097:blood / Q000276:immunology* / Q000652:urine; D051381:Rats; D017208:Rats, Wistar; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism
D000199:Actins; D000906:Antibodies; D003176:Complement C3; D003404:Creatinine; D017228:Hepatocyte Growth Factor; D007518:Isoantibodies; D018809:Proliferating Cell Nuclear Antigen; D011518:Proto-Oncogene Proteins; D020794:Receptor Protein-Tyrosine Kinases; C035678:anti-Thy antibody; C082332:macrophage stimulating protein; C498862:Acta2 protein, rat; C080835:RON protein