Granulation tissue formation during skin wound healing requires the migration and proliferation of dermal fibroblasts in the wound site, where a subsequent remodeling of extracellular matrices (ECM) occurs. An abnormality of ECM remodeling within the healing wound leads to fibrosis and a contracted scar. To evaluate whether acteoside, a phenylethanoid glycoside isolated from the leaves of Rehmannia glutinosa LIBOSCH., exhibits wound-healing actions, we examined the effect of acteoside on the expression of matrix metalloproteinases (MMPs) in normal human dermal fibroblasts (NHDF). Acteoside dose- and time-dependently augmented the activation of the precursor of MMP-2 (proMMP-2/progelatinase A) in untreated- and interleukin-1β-treated NHDF, while the alteration of the MMP-2 gene expression was negligible. The acteoside-induced proMMP-2 activation was associated with the augmented membrane-type 1 MMP (MT1-MMP) expression in the NHDF. In addition, the proMMP-2 activation was enhanced by two aglycones in acteoside: Caffeic acid and 3,4-dihydroxyphenylethanol, which consist of catechol. However, there was no change in the proMMP-2 activation in other catechol derivatives: Homovanillyl alcohol- and homovanillic acid- treated NHDF, indicating that catechols in acteoside were requisite for the regulation of the MMP activation and expression in NHDF. Furthermore, the proMMP-2 activation by acteoside was selectively inhibited by LY294002, a potent phosphatidylinositol-3-kinase (PI3K) inhibitor. These results provide novel evidence that acteoside augments proMMP-2 activation along with an increase in MT1-MMP expression through a PI3K signal pathway in NHDF. Thus, acteoside is likely to be an attractive candidate that facilitates ECM remodeling in the skin wound repair process.
CITATION STYLE
Si, N., Kanazawa, H., Okuyama, K., Imada, K., Wang, H., Yang, J., … Sato, T. (2018). Involvement of catechols in acteoside in the activation of promatrix metalloproteinase-2 and membrane type-1-matrix metalloproteinase expression via a phosphatidylinositol-3-kinase pathway in human dermal fibroblasts. Biological and Pharmaceutical Bulletin, 41(10), 1530–1536. https://doi.org/10.1248/bpb.b18-00107
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