Hepatocyte growth factor increases urokinase-type plasminogen activator (u-PA) and u-PA receptor expression in Madin-Darby canine kidney epithelial cells.

摘要: We have recently demonstrated that fibroblast-conditioned medium induces Madin-Darby canine kidney (MDCK) epithelial cells to form branching tubules when grown in three-dimensional collagen or fibrin gels (Montesano, R., Schaller, G., and Orci, L. (1991) Cell 66, 697-711), this morphogenetic effect is mediated by hepatocyte growth factor (HGF), also known as scatter Matsumoto, K., Nakamura, T., 67, 901-908). In gels, inhibited addition of exogenous serine protease inhibitors, which suggests a role for plasminogen activators (PAs) the matrix remodeling required tubulogenesis. studies reported paper, we investigated (CM) HGF on production PAs MDCK cells. found urokinase-type PA (u-PA) activity mRNA are increased 4.9-fold CM from human MRC-5 fibroblasts, has tubulogenic activity, but not Detroit-550 lacks activity. The u-PA inductive property was completely preincubation with antibodies recombinant (rhHGF). Exogenously added rhHGF 5.9-fold cells, an optimal at approximately 10 ng/ml. receptor 34.9-fold 71% preincubating rhHGF, mimicked exogenously (31.3-fold increase). These results demonstrate HGF, tubulogenesis vitro, increases expression these Taken together our previous observations, resulting increase extracellular proteolysis, appropriately localized cell surface, morphogenesis.