Bradykinin induces matrix metalloproteinase-9 expression and cell migration through a PKC-δ-dependent ERK/Elk-1 pathway in astrocytes

✍ Scribed by Hsi-Lung Hsieh; Cheng-Ying Wu; Chuen-Mao Yang

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 715 KB
• Volume: 56
• Category: Article
• ISSN: 0894-1491
• DOI: 10.1002/glia.20637

✦ Synopsis

Abstract

Many reports have shown that matrix metalloproteinase (MMP)‐9 plays an important role in brain inflammation and diseases. In our previous study, bradykinin (BK) has been shown to induce proMMP‐9 expression via MAPKs and NF‐κB in rat brain astrocytes (RBA‐1). However, the molecular mechanisms and physiological roles underlying BK‐induced MMP‐9 expression in RBA‐1 remain unclear. Here we reported that BK induced proMMP‐9 expression and promoted RBA‐1 cell migration, via a B~2~ BK receptor‐activated protein kinase C‐δ (PKC‐δ)‐dependent signaling pathway. Activation of PKC‐δ led to phosphorylation and translocation of extracellular signal‐regulated kinase 1/2 (ERK1/2) and then activated a transcription factor Elk‐1. Phospho‐Elk‐1 bound to MMP‐9 promoter and thereby induced transcription of MMP‐9. The rat MMP‐9 promoter containing an Elk‐1 cis‐binding site (Ets domain), that located at nucleotides −511 to −506 was identified as a crucial domain linking to BK action. Moreover, BK induced recruitment of p300 (as a transcriptional co‐activator) to the MMP‐9 promoter, leading to the acetylation of histone H4 in chromatin and facilitating MMP‐9 gene transcription. Taken together, these results suggested that in RBA‐1 cells, activation of ERK1/2 by a PKC‐δ‐dependent event mediated through Elk‐1 pathway is essential for MMP‐9 gene up‐regulation and cell migration induced by BK. © 2008 Wiley‐Liss, Inc.