Complex regulation of plasminogen activator inhibitor type-1 (PAI-1) gene expression by serum and substrate adhesion

摘要: Expression of plasminogen activator inhibitor type-1 (PAI-1), a member the serine protease (SERPIN) superfamily that functions to negatively regulate plasmin-based pericellular proteolytic cascade, was induced early after exposure growth-arrested normal rat kidney (NRK) cells serum-containing medium. Increased PAI-1 transcription rapid (evident within 10 min serum addition) and involved immediate-early response kinetics. [3H]Thymidine autoradiography used map time frame expression during synchronous growth cycle. transcript accumulation peaked in mid-G1 phase (approx. 4–6 h post-stimulation) declined prior to, or concomitant with, onset DNA synthetic phase. Serum increased NRK agarose suspension, as well monolayer, culture; induction suspended (similar monolayer culture conditions) also occurred presence cyclohexamide puromycin. The serum-inductive pathway leading gene activation is thus functional regardless adhesive conditions capacity for de novo protein synthesis. amplitude maintenance later stages G1, however, were subject influences. at 4 8 post-stimulation newly adherent cells, moreover, blocked by puromycin, indicating both secondary mechanisms mRNA levels progression through an ‘activated’ G1