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Article

Age Associated Decrease of MT-1 Melatonin Receptor in Human Dermal Skin Fibroblasts Impairs Protection Against UV-Induced DNA Damage

1
Skin Biology & BioActives, R&D, Estée Lauder Companies, Melville, NY 11747, USA
2
Division of Life Science and the State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Hong Kong, China
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(1), 326; https://doi.org/10.3390/ijms21010326
Received: 13 December 2019 / Revised: 20 December 2019 / Accepted: 22 December 2019 / Published: 3 January 2020
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
The human body follows a physiological rhythm in response to the day/night cycle which is synchronized with the circadian rhythm through internal clocks. Most cells in the human body, including skin cells, express autonomous clocks and the genes responsible for running those clocks. Melatonin, a ubiquitous small molecular weight hormone, is critical in regulating the sleep cycle and other functions in the body. Melatonin is present in the skin and, in this study, we showed that it has the ability to dose-dependently stimulate PER1 clock gene expression in normal human dermal fibroblasts and normal human epidermal keratinocytes. Then we further evaluated the role of MT-1 melatonin receptor in mediating melatonin actions on human skin using fibroblasts derived from young and old subjects. Using immunocytochemistry, Western blotting and RT-PCR, we confirmed the expression of MT-1 receptor in human skin fibroblasts and demonstrated a dramatic age-dependent decrease in its level in mature fibroblasts. We used siRNA technology to transiently knockdown MT-1 receptor in fibroblasts. In these MT-1 knockdown cells, UV-dependent oxidative stress (H2O2 production) was enhanced and DNA damage was also increased, suggesting a critical role of MT-1 receptor in protecting skin cells from UV-induced DNA damage. These studies demonstrate that the melatonin pathway plays a pivotal role in skin aging and damage. Moreover, its correlation with skin circadian rhythm may offer new approaches for decelerating skin aging by modulating the expression of melatonin receptors in human skin. View Full-Text
Keywords: aging; circadian rhythm; melatonin; skin fibroblasts; ultraviolet (UV) irradiation aging; circadian rhythm; melatonin; skin fibroblasts; ultraviolet (UV) irradiation
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MDPI and ACS Style

Dong, K.; Goyarts, E.; Rella, A.; Pelle, E.; Wong, Y.H.; Pernodet, N. Age Associated Decrease of MT-1 Melatonin Receptor in Human Dermal Skin Fibroblasts Impairs Protection Against UV-Induced DNA Damage. Int. J. Mol. Sci. 2020, 21, 326. https://doi.org/10.3390/ijms21010326

AMA Style

Dong K, Goyarts E, Rella A, Pelle E, Wong YH, Pernodet N. Age Associated Decrease of MT-1 Melatonin Receptor in Human Dermal Skin Fibroblasts Impairs Protection Against UV-Induced DNA Damage. International Journal of Molecular Sciences. 2020; 21(1):326. https://doi.org/10.3390/ijms21010326

Chicago/Turabian Style

Dong, Kelly, Earl Goyarts, Antonella Rella, Edward Pelle, Yung H. Wong, and Nadine Pernodet. 2020. "Age Associated Decrease of MT-1 Melatonin Receptor in Human Dermal Skin Fibroblasts Impairs Protection Against UV-Induced DNA Damage" International Journal of Molecular Sciences 21, no. 1: 326. https://doi.org/10.3390/ijms21010326

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