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Updated: Jul 15, 2026
Phenotypic Characterization of Macrophages from Rat Kidney by Flow Cytometry
Published on: October 18, 2016
Neutralization of macrophage-stimulating protein ameliorates renal injury in anti-thy 1 glomerulonephritis
Teresa Rampino1, Grazia Soccio, Marilena Gregorini
1Unit 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
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.
Insights
The macrophage-stimulating protein (MSP)/receptor origin nantaise (RON) pathway plays a key role in anti-Thy 1 nephritis. Blocking MSP reduces kidney damage and cell infiltration in this glomerular disease.
Area of Science:
- Nephrology
- Immunology
- Cell Biology
Background:
- Macrophage-stimulating protein (MSP) is a scatter factor promoting cell proliferation and migration.
- Receptor origin nantaise (RON) is the receptor for MSP, expressed on macrophages and mesangial cells.
- MSP is produced by renal tubular cells, and its role in glomerular disease is unclear.
Purpose of the Study:
- To investigate the role of the MSP/RON system in the pathogenesis of anti-Thy 1 nephritis.
- To determine if MSP/RON signaling contributes to monocyte infiltration and mesangial cell proliferation in glomerular disease.
Main Methods:
- In vivo studies using rats with anti-Thy 1 nephritis, treated with a neutralizing anti-MSP antibody.
- In vitro studies assessing RON expression on monocytes and MSP's chemotactic effect on them.
- Analysis of renal function, histopathology, glomerular injury, and cell infiltration.
Main Results:
- MSP was expressed de novo in glomeruli during anti-Thy 1 disease.
- Neutralization of MSP attenuated serum creatinine rise, proteinuria, and glomerular injury.
- MSP neutralization inhibited neutrophil and monocyte influx and mesangial cell overgrowth.
- LPS stimulation induced de novo RON expression on monocytes, which were attracted by MSP.
Conclusions:
- The MSP/RON system plays a pathogenic role in anti-Thy 1 nephritis.
- Targeting the MSP/RON pathway may offer a therapeutic strategy for glomerular diseases.
