Effect of cyclic AMP on urokinase-type plasminogen activator receptor and fibrinolytic factors in a human osteoblast-like cell line

摘要

We investigated the effect of cyclic AMP (cAMP) on the pericellular fibrinolytic system in NY cells. Dibutyryl cAMP (dbcAMP) or forskolin increased the level of urokinase-type plasminogen activator (u-PA) mRNA and enhanced the secretion of u-PA antigen into the conditioned medium. These agents also increased u-PA antigen on the cell surface. PA inhibitor-1 (PAI-1) antigen was inhibited by dbcAMP or forskolin. Butyrate had no effect on the production and secretion of u-PA and PAI-1. A binding assay of 125I-DFP-u-PA to NY cells revealed a single class of binding sites with a Kd of 3.85 nM and Bmax of 0.89 · 105 binding sites/cell. The Bmax was increased by dbcAMP (1 mM or 10 mM), forskolin (2 μM or 20 μM) of 1.0-, 1.4-, 1.2- and 1.8-fold, respectively. However, the Kd value was not changed. Furthermore, the level of mRNA for the u-PA receptor (u-PAR) was increased by these agents 1.2-, 1.7-, 1.8- and 2.5-fold, respectively. However, butyrate did not alter either the Bmax or the u-PAR mRNA level. These results indicated that the pericellular fibrinolytic activity induced by u-PA/u-PAR is modulated by cAMP in osteoblast-like cells.