Macrophage stimulating protein may promote tubular regeneration after acute injury.
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.
Cantaluppi
Vincenzo
V
Research Center for Experimental Medicine, Department of Internal Medicine, University of Torino, Torino, Italy.
Biancone
Luigi
L
Romanazzi
Giuseppe Mauriello
GM
Figliolini
Federico
F
Beltramo
Silvia
S
Galimi
Francesco
F
Camboni
Maria Gavina
MG
Deriu
Elisa
E
Conaldi
Piergiulio
P
Bottelli
Antonella
A
Orlandi
Viviana
V
Herrera
Maria Beatriz
MB
Pacitti
Alfonso
A
Segoloni
Giuseppe Paolo
GP
Camussi
Giovanni
G
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*
D011518:Proto-Oncogene Proteins; C082332:macrophage stimulating protein; D017228:Hepatocyte Growth Factor; C080835:RON protein; D020794:Receptor Protein-Tyrosine Kinases