The Anti-Wrinkle Mechanism of Melatonin in UVB Treated HaCaT Keratinocytes and Hairless Mice via Inhibition of ROS and Sonic Hedgehog Mediated Inflammatory Proteins

• Published in: International journal of molecular sciences Vol. 19; no. 7; p. 1995
• Main Authors: Park, Eun Kyung, Lee, Hyo-Jung, Lee, Hyemin, Kim, Ju-Ha, Hwang, Jisung, Koo, Ja Il, Kim, Sung-Hoon
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 08.07.2018; MDPI
• Subjects: Animals; Butyl hydroperoxide; Cell Line; Collagen; Cox-2; Cyclooxygenase-2; Cytotoxicity; Extracellular signal-regulated kinase; HaCaT keratinocytes; Hairless; hedgehog; Hedgehog protein; Hedgehog Proteins - metabolism; Humans; Inflammation; Interstitial collagenase; Keratinocytes; Keratinocytes - cytology; Keratinocytes - drug effects; Keratinocytes - metabolism; Keratinocytes - radiation effects; Matrix metalloproteinase; Melatonin; Melatonin - administration & dosage; Melatonin - pharmacology; Metalloproteinase; Mice; Mice, Hairless; MMP-1; NF-κB protein; Oxidative Stress - drug effects; Proteins; Reactive Oxygen Species - metabolism; Rodents; ROS; Signal Transduction - drug effects; Signal Transduction - radiation effects; Skin; Skin Aging - drug effects; tert-Butylhydroperoxide - adverse effects; Ultraviolet radiation; Ultraviolet Rays - adverse effects; UVB; Water loss; HaCaT keratinocytes; UVB; hedgehog; Cox-2; MMP-1; ROS; collagen; melatonin
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms19071995

Though melatonin is known to improve ultraviolet B (UVB)-induced oxidative damage and inflammatory conditions via the blockade of the nuclear factor (NF)-κB, interleukin (IL)-6, there is no report on the anti-wrinkle effect of melatonin to date. Hence in the present study, the anti-wrinkle mechanism of melatonin was elucidated in UVB treated HaCaT keratinocytes and hairless mice. Herein melatonin protected against a radical initiator tert-Butyl hydroperoxide (t-BOOH) induced reactive oxygen species (ROS) production, matrix metalloprotease 1 (MMP-1), pro-collagen and cytotoxicity in HaCaT keratinocytes. Additionally, melatonin suppressed the expression of sonic hedgehog (SHH) and GLI1 for hedgehog signaling and p-NF-κB, cyclooxygenase (COX-2), phospho-extracellular signal-regulated kinase-1 (p-ERK) for inflammatory responses in UVB treated HaCaT keratinocytes. Furthermore, melatonin protected skin from wrinkle formation, transdermal water loss in hairless mice irradiated by UVB for 8 weeks. Notably, melatonin prevented against epidermal thickness and dermal collagen degradation in UVB irradiated hairless mice by Hematoxylin and Eosin and Masson's trichrome staining. Taken together, these findings suggest that melatonin reduces wrinkle formation via inhibition of ROS/SHH and inflammatory proteins such as NF-κB/COX-2/ERK/MMP1.