Macrophage-stimulating protein is produced by tubular cells and activates mesangial cells.
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.
Rampino
Teresa
T
*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.
Collesi
Chiara
C
*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.
Gregorini
Marilena
M
*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.
Maggio
Milena
M
*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.
Soccio
Grazia
G
*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.
Guallini
Paola
P
*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.
Canton
Antonio Dal
AD
*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.
D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D005920:Glomerular Mesangium / Q000166:cytology / Q000502:physiology*; D006133:Growth Substances / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D017228:Hepatocyte Growth Factor; D006801:Humans; D007678:Kidney Glomerulus / Q000378:metabolism; D007684:Kidney Tubules / Q000166:cytology / Q000502:physiology*; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D012016:Reference Values
D006133:Growth Substances; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C082332:macrophage stimulating protein; D017228:Hepatocyte Growth Factor; C080835:RON protein; D020794:Receptor Protein-Tyrosine Kinases