Macrophage Stimulating Protein May Promote Tubular Regeneration after Acute Injury

• Published in: Journal of the American Society of Nephrology Vol. 19; no. 10; pp. 1904 - 1918
• Main Authors: CANTALUPPI, Vincenzo, BIANCONE, Luigi, ORLANDI, Viviana, HERRERA, Maria Beatriz, PACITTI, Alfonso, PAOLO SEGOLONI, Giuseppe, CAMUSSI, Giovanni, ROMANAZZI, Giuseppe Mauriello, FIGLIOLINI, Federico, BELTRAMO, Silvia, GALIMI, Francesco, GAVINA CAMBONI, Maria, DERIU, Elisa, CONALDI, Piergiulio, BOTTELLI, Antonella
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01.10.2008; American Society of Nephrology
• Subjects: Acute Kidney Injury - blood; Aged; Animals; Basic Research; Biological and medical sciences; Case-Control Studies; Cell Culture Techniques; Cell Survival; Critical Illness; Hepatocyte Growth Factor - blood; Humans; Kidney Transplantation; Kidney Tubules - physiology; Kidneys; Medical sciences; Mice; Mice, Inbred C57BL; Middle Aged; Nephrology. Urinary tract diseases; Proto-Oncogene Proteins - blood; Receptor Protein-Tyrosine Kinases - blood; Regeneration - physiology; Urinary system involvement in other diseases. Miscellaneous; Kidney disease; Human; Regeneration; Nephrology; Renal tubule; Urinary system disease; Acute kidney injury; Macrophage stimulating protein; Urology
• ISSN: 1046-6673; 1533-3450
• DOI: 10.1681/asn.2007111209

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.