Essential Role for c-jun N-terminal Kinase on tPA-induced Matrix Metalloproteinase-9 Regulation in Rat Astrocytes

다국어 초록 (Multilingual Abstract)

Tissue plasminogen activator (tPA) is used to lyseclots and reperfuse brain in ischemic stroke. However, side-effects of intracerebral hemorrhage (ICH) and edema limittheir clinical application. In part, these phenomena has beenlinked with elevations in matrix metalloproteinase-9 (MMP-9) in neurovascular unit. However little is known about theirregulatory signaling pathways in brain cells. Here, I examinethe role of MAP kinase pathways in tPA-induced MMP-9g/ml) induceddose-dependent elevations in MMP-9 and MMP-2 inconditioned media. Although tPA increased phosphorylationin two MAP kinases (ERK, JNK), only inhibition of the JNKpathway by the JNK inhibitor SP600126 significantly reducedMMP-9 upregulation. Neither ERK inhibition with U0126 norp38 inhibition with SB203580 had any significant effects.Taken together, these results suggest that c-jun N-terminalkinase (JNK) plays an essential role for tPA-induced MMP-9upregulation.

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