ISSN:
1524-475X
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Matrix metalloproteinase-9 (MMP-9) transiently expresses in acute wound. In non-healed wounds, MMP-9 together with other proteinases persistently elevate, which may lead excessive ECM degradation and failure of wound closure. To understand the molecular regulation of MMP-9 we investigated the signal transduction for TNF-alpha mediated induction of MMP-9 by dermal fibroblasts. TNF-alpha initiates three major signal pathways including NF-11B, JUN N-terminal kinase (JNK), and p38 MAPK. On the other hand, Rho-GTPase plays an important role in a variety of cellular functions including cell morphogenesis, motility, survival, angiogenesis, and mitosis. It remains unknown if the “cross talk” of these signals having a role in regulation of matrix metalloproteinases (MMPs). In this study we found that over expression of the p21-activated kinase (PAK) specifically attenuates TNF-alpha mediated induction of MMP-9. However, TNF-alpha mediated induction of MMP-3 and proMMP-2 activation was intact. NF-κB signal is regarded as a common pathway for many MMPs. Indeed, PAK did not affect TNF-alpha mediated degradation of Ikappa B, suggesting additional signal is targeted by PAK. In contrast, MMP-3 but not MMP-9 expression is specifically blocked by p38 MAK. Thus TNF-alpha induced expression of multiple MMPs in wound healing may utilize different intracellular signal pathways.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.1067-1927.2004.0abstractxq.x
Permalink
