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Blockade of endothelial matrix metalloproteinase activation by isoliquiritigenin: involvement of p38 MAPK
Author(s) -
Kang Sang Wook,
Choi YeanJung,
Choi JungSuk,
Kwon HyangMi,
Bae JiYoung,
Kang YoungHee
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1098-a
The aberrant expression of matrix metalloproteinases (MMP) has been implicated in the angiogenesis leading to matrix degradation and in the destabilization of atherosclerotic plaques. Activation or suppression of MAPK‐responsive intracellular signaling pathways has been linked to MMP activation in various experimental models. Our previous study showed that isoliquiritigenin, a licorice pigment component, suppressed phorbol 12‐myristate 13‐acetate (PMA)‐induced MMP production in human endothelial cells in vitro. This study investigated whether a p38 MAPK‐responsive mechanism is responsible for this suppression. We found that isoliquiritigenin at ≥1 μM markedly suppressed expression of membrane type1‐matrix metalloproteinase (MT1‐MMP) induced by PMA as well as expression of MMP‐2 and MMP‐9 in a dose‐dependent manner. Isoliquiritigenin rapidly prevented PMA‐stimulated phosphorylation of p38 MAPK within 30 min after its treatment. The results demonstrate that isoliquiritigenin blocked PMA‐dependent and p38 MAPK‐responsive pathways leading to a direct activation of endothelial MMP. Isoliquiritigenin‐mediated inhibition of MMP may boost a therapeutic efficacy during angiogenesis and atherogenesis. Supported by Brain Korea 21 (2006).