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Published on: January 22, 2019
Matrine inhibits PMA-induced MMP-1 expression in human dermal fibroblasts
Eunsun Jung1, Jongsung Lee, Sungran Huh
1Biospectrum Life Science Institute, Gunpo City, Republic of Korea.
Abstract:
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.
Insights
Matrine, a natural compound, inhibits matrix metalloproteinase-1 (MMP-1) expression in human skin cells. This suggests matrine may help treat inflammatory skin disorders by targeting the AP-1 signaling pathway.
Area of Science:
- Biochemistry
- Dermatology
- Pharmacology
Background:
- Matrix metalloproteinase-1 (MMP-1) is crucial for extracellular matrix (ECM) turnover.
- ECM remodeling by MMPs is implicated in various physiological and pathological conditions.
- Understanding MMP-1 regulation is key for developing therapeutic strategies.
Purpose of the Study:
- To investigate the therapeutic potential of matrine.
- To determine matrine's effect on MMP-1 expression in human dermal fibroblasts.
- To elucidate the mechanism by which matrine modulates MMP-1 expression.
Main Methods:
- Human dermal fibroblast cells were treated with matrine and phorbol myristate acetate (PMA).
- MMP-1 mRNA and protein levels were assessed.
- AP-1 promoter activity and mitogen-activated protein kinase (MAPK) phosphorylation were analyzed.
Main Results:
- Matrine significantly inhibited PMA-induced MMP-1 mRNA and protein expression.
- Matrine suppressed PMA-induced activation of the AP-1 promoter.
- Matrine inhibited the phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), but not p38 kinase.
Conclusions:
- Matrine suppresses PMA-induced MMP-1 expression via inhibition of the AP-1 signaling pathway.
- Matrine's mechanism involves downregulating ERK and JNK phosphorylation.
- Matrine shows potential therapeutic benefits for inflammatory skin disorders.
