title: Macrophage stimulating protein may promote tubular regeneration after acute injury.
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.
authors.affiliation: Research Center for Experimental Medicine, Department of Internal Medicine, University of Torino, Torino, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cantaluppi
authors.forename: Luigi
authors.initials: L
authors.lastname: Biancone
authors.forename: Giuseppe Mauriello
authors.initials: GM
authors.lastname: Romanazzi
authors.forename: Federico
authors.initials: F
authors.lastname: Figliolini
authors.forename: Silvia
authors.initials: S
authors.lastname: Beltramo
authors.forename: Francesco
authors.initials: F
authors.lastname: Galimi
authors.forename: Maria Gavina
authors.initials: MG
authors.lastname: Camboni
authors.forename: Elisa
authors.initials: E
authors.lastname: Deriu
authors.forename: Piergiulio
authors.initials: P
authors.lastname: Conaldi
authors.forename: Antonella
authors.initials: A
authors.lastname: Bottelli
authors.forename: Viviana
authors.initials: V
authors.lastname: Orlandi
authors.forename: Maria Beatriz
authors.initials: MB
authors.lastname: Herrera
authors.forename: Alfonso
authors.initials: A
authors.lastname: Pacitti
authors.forename: Giuseppe Paolo
authors.initials: GP
authors.lastname: Segoloni
authors.forename: Giovanni
authors.initials: G
authors.lastname: Camussi
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood*; D000368:Aged; D000818:Animals; D016022:Case-Control Studies; D018929:Cell Culture Techniques; D002470:Cell Survival; D016638:Critical Illness; D017228:Hepatocyte Growth Factor / Q000097:blood*; D006801:Humans; D016030:Kidney Transplantation; D007684:Kidney Tubules / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000097:blood*; D020794:Receptor Protein-Tyrosine Kinases / Q000097:blood*; D012038:Regeneration / Q000502:physiology*
chemical_list: D011518:Proto-Oncogene Proteins; C082332:macrophage stimulating protein; D017228:Hepatocyte Growth Factor; C080835:RON protein; D020794:Receptor Protein-Tyrosine Kinases