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(American Journal of Pathology. 2001;159:1275-1285.)
© 2001 American Society for Investigative Pathology

Regular Articles

Hepatocyte Growth Factor/Scatter Factor Released during Peritonitis Is Active on Mesothelial Cells

Teresa Rampino^*, Giovanni Cancarini, Marilena Gregorini^*, Paola Guallini^*, Milena Maggio^*, Andrea Ranghino^*, Grazia Soccio^* and Antonio Dal Canton^*

From the Unità di Nefrologia Dialisi e Trapianto,^*
Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo ed Università di Pavia, Pavia; and the Unità di Nefrologia,
Spedali Civili ed Università di Brescia, Brescia, Italy

Peritonitis causes mesothelial detachment that may result in persistent peritoneal denudation and fibrosis. We investigated whether hepatocyte growth factor (HGF), a scatter factor that induces detachment from substrate and fibroblastic transformation of several cell types, is produced during peritonitis and is active on mesothelial cells. We studied 18 patients on peritoneal dialysis, 9 uncomplicated, 9 with peritonitis. HGF was measured in serum, peritoneal fluid, and supernatant of peripheral blood mononuclear cells and peritoneal mononuclear cells. Primary culture of human peritoneal mesothelial cells and the human mesothelial cell line MeT-5A were conditioned with recombinant HGF, serum, and peritoneal fluid. HGF levels were significantly higher in serum and peritoneal fluid of peritonitic than uncomplicated patients. Mononuclear cells of peritonitic patients produced more HGF than cells of uncomplicated patients. Recombinant HGF, serum, and peritoneal fluid of peritonitic patients caused mesothelial cell growth, detachment, transformation from epithelial to fibroblast-like shape, overexpression of vimentin, and synthesis of type I and III collagen. In conclusion, HGF released during peritonitis causes a change in mesothelial cell phenotype and function. HGF may affect the healing process facilitating repair through mesothelial cell growth, but may contribute to peritoneal fibrosis inducing cell detachment with mesothelial denudation and collagen synthesis.

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