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J Invest Dermatol. 2013 Apr;133(4):919-28. doi: 10.1038/jid.2012.383. Epub 2012 Oct 25.

Suppression of UV-induced wrinkle formation by induction of HSP70 expression in mice.

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Department of Analytical Chemistry, Keio University, Tokyo, Japan.


UV-induced wrinkle formation owing to the degeneration of the extracellular matrix (ECM) is a major dermatological problem in which abnormal activation of matrix metalloproteinases (MMPs) and elastases have important roles. Heat shock protein 70 (HSP70) has cytoprotective and anti-inflammatory activities. In this study, we examined the effect of HSP70 expression on UV-induced wrinkle formation. Mild heat treatment (exposure to heated water at 42 °C) of the dorsal skin of hairless mice induced the expression of HSP70. The long-term repeated exposure to UV induced epidermal hyperplasia, decreased skin elasticity, degeneration of ECM, and wrinkle formation, which could be suppressed in mice concomitantly subjected to this heat treatment. The UV-induced epidermal hyperplasia, decreased skin elasticity, and degeneration of ECM were less apparent in transgenic mice expressing HSP70 than in wild-type mice. UV-induced fibroblast cell death, infiltration of inflammatory cells, and activation of MMPs and elastase in the skin were also suppressed in the transgenic mice. This study provides evidence for an inhibitory effect of HSP70 on UV-induced wrinkle formation. The results suggest that this effect is mediated by various properties of HSP70, including its cytoprotective and anti-inflammatory activities. We propose that HSP70 inducers used in a clinical context could prove beneficial for the prevention of UV-induced wrinkle formation.

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