Tissue-type plasminogen activator acts as a cytokine that triggers intracellular signal transduction and induces matrix metalloproteinase-9 gene expression.

摘要: Tissue-type plasminogen activator (tPA), a serine protease well known for generating plasmin, has been demonstrated to induce matrix metalloproteinase-9 (MMP-9) gene expression and protein secretion in renal interstitial fibroblasts. However, exactly how tPA transduces its signal into the nucleus control is unknown. This study investigated mechanism by which induces MMP-9 expression. Both wild-type non-enzymatic mutant were found rat kidney fibroblasts (NRK-49F), indicating that actions of are independent proteolytic activity. bound low density lipoprotein receptor-related protein-1 (LRP-1) NRK-49F cells, this binding was competitively abrogated LRP-1 antagonist, receptor-associated protein. In mouse embryonic (PEA-13) lacking LRP-1, failed Furthermore, induced rapid tyrosine phosphorylation on β subunit followed activation Mek1 downstream Erk-1 -2. Blockade Erk-1/2 inhibitor abolished induction cells. Conversely, overexpression constitutively activated obstructed kidney, tPA, concomitantly interstitium. Collectively, these results suggest besides classical activity, acts as cytokine binds cell membrane receptor phosphorylation, triggers intracellular transduction, thereby inducing specific