Abstract
We investigated whether cilostazol, an activator of cyclic adenosine monophosphate (cAMP)-dependent intracellular signaling, could inhibit ultraviolet B (UVB) irradiation-induced photoaging in HR-1 hairless mice. Cilostazol decreased wrinkle formation and skin thickness in UVB-irradiated mice, as well as increased staining of collagen fibers and inhibition of reactive oxygen species (ROS) formation in the skin. Moreover, the proteolytic activities of gelatinase matrix metalloproteinase (MMP)-9 and collagenase MMP-3 were significantly decreased in UVB-irradiated mice treated with cilostazol. Western blotting showed that UVB-induced activation of p38 mitogen-activated protein kinases (MAPK) and nuclear factor (NF)-κB was significantly inhibited by cilostazol, whereas the activation of Akt was significantly enhanced by cilostazol. Confirmation of localized protein expression in the skin revealed marked p38 MAPK and NF-κB activation that was mainly detected in the dermis. Marked Akt activation was mainly detected in the epidermis. Our results suggest that cilostazol may have anti-photoaging effects on UVB-induced wrinkle formation by maintaining the extracellular matrix density in the dermis, which occurs via regulation of ROS and related p38 MAPK and NF-κB signaling, and subsequent down-regulation of MMPs. Therefore, cilostazol may protect against photoaging-induced wrinkle formation.
Highlights
We investigated whether cilostazol, an activator of cyclic adenosine monophosphatedependent intracellular signaling, could inhibit ultraviolet B (UVB) irradiation-induced photoaging in HR-1 hairless mice
Generation of reactive oxygen species (ROS) in the skin plays a critical role in the mitogen-activated protein kinases (MAPK) and phosphatidylinositol-3 kinase (PI3K)/Akt-mediated signaling pathways triggered by ultraviolet rays (UV) radiation[4,7,8,9]
Reduced flakiness and roughness were observed in UVB-irradiated mice treated with cilostazol compared that in mice exposed to UVB irradiation alone (Fig. 1A)
Summary
An activator of cyclic adenosine monophosphate (cAMP)dependent intracellular signaling, could inhibit ultraviolet B (UVB) irradiation-induced photoaging in HR-1 hairless mice. Generation of ROS in the skin plays a critical role in the mitogen-activated protein kinases (MAPK) and phosphatidylinositol-3 kinase (PI3K)/Akt-mediated signaling pathways triggered by UV radiation[4,7,8,9]. These kinases stimulate the transcription factors activator protein (AP)-1 and nuclear factor (NF)- κB10,11, and participate in the induction of MMP activation[5,6], leading to wrinkle formation in photoaged skin[12,13]. We hypothesized that cilostazol might have protective properties against skin www.nature.com/scientificreports/
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