1. Macrophage stimulating protein may promote tubular regeneration after acute injury.
- Author
-
Cantaluppi V, Biancone L, Romanazzi GM, Figliolini F, Beltramo S, Galimi F, Camboni MG, Deriu E, Conaldi P, Bottelli A, Orlandi V, Herrera MB, Pacitti A, Segoloni GP, and Camussi G
- Subjects
- Aged, Animals, Case-Control Studies, Cell Culture Techniques, Cell Survival, Critical Illness, Humans, Mice, Mice, Inbred C57BL, Middle Aged, Acute Kidney Injury blood, Hepatocyte Growth Factor blood, Kidney Transplantation, Kidney Tubules physiology, Proto-Oncogene Proteins blood, Receptor Protein-Tyrosine Kinases blood, Regeneration physiology
- Abstract
Macrophage-stimulating protein (MSP) exerts proliferative and antiapoptotic effects, suggesting that it may play a role in tubular regeneration after acute kidney injury. In this study, elevated plasma levels of MSP were found both in critically ill patients with acute renal failure and in recipients of renal allografts during the first week after transplantation. In addition, MSP and its receptor, RON, were markedly upregulated in the regenerative phase after glycerol-induced tubular injury in mice. In vitro, MSP stimulated tubular epithelial cell proliferation and conferred resistance to cisplatin-induced apoptosis by inhibiting caspase activation and modulating Fas, mitochondrial proteins, Akt, and extracellular signal-regulated kinase. MSP also enhanced migration, scattering, branching morphogenesis, tubulogenesis, and mesenchymal de-differentiation of surviving tubular cells. In addition, MSP induced an embryonic phenotype characterized by Pax-2 expression. In conclusion, MSP is upregulated during the regeneration of injured tubular cells, and it exerts multiple biologic effects that may aid recovery from acute kidney injury.
- Published
- 2008
- Full Text
- View/download PDF