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Macrophage-stimulating protein is produced by tubular cells and activates mesangial cells
Teresa Rampino1, Chiara Collesi1, Marilena Gregorini1
1*Unit of Nephrology, Dialysis and Transplant, I. R. C. C. S. Policlinico San Matteo and University, Pavia, Italy; and Institute for Cancer Research and Treatment, Torino, Italy.
Abstract:
Until now, hepatocytes have been the only known cell source of macrophage-stimulating protein (MSP), and tissue macrophages have been the cells on which the biologic effects of MSP have been proved. To extend the understanding of the biologic meaning of MSP, it was investigated whether MSP operates in the kidney. MSP protein was evaluated by Western blot in supernatant of cultured human tubular cells (HK2) and human mesangial cells (HMC). MSP mRNA was investigated in HK2 by reverse transcription-polymerase chain reaction (RT-PCR). The expression of the MSP receptor, RON, was evaluated in HMC and HK2 by Western blot. RON mRNA was investigated in HMC by RT-PCR. The expression of MSP and RON in normal human renal tissue was studied by immunohistochemistry. HMC were stimulated with recombinant MSP (rMSP) and HK2 supernatant to study cell growth, migration, and the capacity to invade an artificial collagen matrix and synthesize interleukin-6 (IL-6). HK2 produced MSP and expressed RON in a form that was phosphorylated by rMSP. HMC expressed RON but did not produce MSP. MSP in HK2 supernatant and rMSP induced in HMC phosphorylation of RON, growth, migration, invasion, and IL-6 synthesis. In normal human kidney, tubules expressed MSP and RON. These results indicate a novel field of operation for MSP and suggest a pathogenic role of the MSP/RON system in renal disease. In fact, MSP released by tubular cells may recruit monocytes/macrophages in inflammatory tubulointerstitial disorders. In addition, MSP either circulating or as paracrine product may sustain glomerular mesangioproliferative disease.
Insights
Macrophage-stimulating protein (MSP) is produced by kidney tubular cells and acts on mesangial cells, suggesting a role in kidney diseases like tubulointerstitial disorders and glomerulonephritis.
Area of Science:
- Nephrology
- Cell Biology
- Immunology
Background:
- Macrophage-stimulating protein (MSP) was previously known to be produced by hepatocytes and act on tissue macrophages.
- The role and function of MSP within the kidney remained largely unexplored.
- Understanding novel cellular sources and targets of MSP is crucial for kidney disease research.
Purpose of the Study:
- To investigate the presence and function of MSP and its receptor, RON, in the human kidney.
- To determine if kidney cells produce MSP and express RON.
- To elucidate the potential role of the MSP/RON system in renal pathophysiology.
Main Methods:
- Western blot and RT-PCR were used to evaluate MSP and RON expression in cultured human tubular (HK2) and mesangial (HMC) cells.
- Immunohistochemistry was employed to study MSP and RON expression in normal human renal tissue.
- Functional assays assessed the effects of MSP on HMC growth, migration, invasion, and IL-6 synthesis.
Main Results:
- Human kidney tubular cells (HK2) produce MSP and express the MSP receptor, RON.
- Human mesangial cells (HMC) express RON but do not produce MSP.
- MSP stimulation induced RON phosphorylation, growth, migration, invasion, and IL-6 synthesis in HMC.
Conclusions:
- The study identifies kidney tubular cells as a novel source of MSP.
- The MSP/RON system operates within the kidney, influencing mesangial cell behavior.
- This system may play a pathogenic role in renal diseases, including inflammatory tubulointerstitial disorders and mesangioproliferative glomerulonephritis.