Low-dose UVB irradiation stimulates matrix metalloproteinase-1 expression via a BLT2-linked pathway in HaCaT cells
- Authors
- Kim, Cheolmin; Ryu, Ho-Cheol; Kim, Jae-Hong
- Issue Date
- 31-Dec-2010
- Publisher
- NATURE PUBLISHING GROUP
- Keywords
- 12-hydroxy-5,8,10,14-eicosatetraenoic acid; leukotriene B-4; LTB(4)R2 protein, human; matrix metalloproteinase 1; reactive oxygen species; skin aging; ultraviolet rays
- Citation
- EXPERIMENTAL AND MOLECULAR MEDICINE, v.42, no.12, pp.833 - 841
- Indexed
- SCIE
SCOPUS
KCI
- Journal Title
- EXPERIMENTAL AND MOLECULAR MEDICINE
- Volume
- 42
- Number
- 12
- Start Page
- 833
- End Page
- 841
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/115089
- DOI
- 10.3858/emm.2010.42.12.086
- ISSN
- 1226-3613
- Abstract
- Skin exposure to low-dose ultraviolet B (UVB) light up-regulates the expression of matrix metalloproteinase-1 (MMP-1), thus contributing to premature skin aging (photo-aging). Although cyclooxygenase-2 (COX-2) and its product, prostaglandin E-2 (PGE(2)), have been associated with UVB-induced signaling to MMP expression, very little are known about the roles of lip-oxygenases and their products, especially leukotriene B-4 (LTB4) and 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE), in MMP-1 expression in skin keratinocytes. In the present study, we demonstrate that BLT2, a cell surface receptor for LTB4 and 12(S)-HETE, plays a critical role in UVB-mediated MMP-1 upregulation in human HaCaT keratinocytes. Moreover, our results demonstrated that BLT2-mediated MMP-1 upregulation occurs through a signaling pathway dependent on reactive oxygen species (ROS) production and the subsequent stimulation of ERK. Blockage of BLT2 via siRNA knockdown or with the BLT2-antagonist LY255283 completely abolished the up-regulated expression of MMP-1 induced by low-dose UVB irradiation. Finally, when HaCaT cells were transiently transfected with a BLT2 expression plasmid, MMP-1 expression was significantly enhanced, along with ERK phosphorylation, suggesting that BLT2 overexpression alone is sufficient for MMP-1 up-regulation. Together, our results suggest that the BLT2-ROS-ERK-linked cascade is a novel signaling mechanism for MMP-1 upregulation in low-dose UVB- irradiated keratinocytes and thus potentially contributes to photo-aging.
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Collections - College of Life Sciences and Biotechnology > Division of Life Sciences > 1. Journal Articles
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