Jung Eunsun, Lee Jongsung, Huh Sungran, Lee Jienny, Hwang Hyunjin, Kim Youngsoo, Kim Yong-Woo, Byun Sang Yo, Park Deokhoon
Biospectrum Life Science Institute, Gunpo City, Republic of Korea.
Biofactors. 2008;33(2):121-8. doi: 10.1002/biof.5520330204.
Matrix metalloproteinase-1 (MMP-1) plays an important role in the maintenance and turnover of extracellular matrix (ECM) macromolecules. Remodelling of extracellular matrix by MMPs is a hallmark feature of physiological and pathological processes. In this study, in order to establish the therapeutic potential of matrine, we investigated its effect on MMP-1 expression in human dermal fibroblast cells. We found that matrine inhibited both MMP-1 mRNA and protein expression induced by PMA (phorbol myristate acetate). Therefore, we characterized the inhibitory mechanism of matrine on PMA-induced MMP-1 expression. Matrine inhibited PMA-induced activation of the AP-1 promoter, an important nuclear transcription factor in MMP-1 expression. Additionally, we detected that matrine suppressed the PMA-induced phosphorylation of two mitogen-activated protein kinases, extracellular signal-regulated protein kinase and c-Jun N-terminal kinase, but did not suppress the PMA-induced phosphorylation of p38 kinase. These results suggest that matrine suppresses PMA-induced MMP-1 expression through inhibition of the AP-1 signaling pathway and also may be beneficial for treatment of some inflammatory skin disorders.
基质金属蛋白酶-1（MMP-1）在细胞外基质（ECM）大分子的维持和更新中发挥着重要作用。MMPs对细胞外基质的重塑是生理和病理过程的一个标志性特征。在本研究中，为了确定苦参碱的治疗潜力，我们研究了其对人皮肤成纤维细胞中MMP-1表达的影响。我们发现苦参碱抑制了由佛波酯（PMA）诱导的MMP-1 mRNA和蛋白表达。因此，我们对苦参碱抑制PMA诱导的MMP-1表达的机制进行了表征。苦参碱抑制了PMA诱导的AP-1启动子的激活，AP-1是MMP-1表达中的一种重要核转录因子。此外，我们检测到苦参碱抑制了PMA诱导的两种丝裂原活化蛋白激酶（细胞外信号调节蛋白激酶和c-Jun N末端激酶）的磷酸化，但没有抑制PMA诱导的p38激酶的磷酸化。这些结果表明，苦参碱通过抑制AP-1信号通路来抑制PMA诱导的MMP-1表达，并且可能对某些炎症性皮肤病的治疗有益。
