Ergothioneine alleviates senescence of fibroblasts induced by UVB damage of keratinocytes via activation of the Nrf2/HO-1 pathway and HSP70 in keratinocytes

Journal Article · Mon Mar 15 04:00:00 EDT 2021 · Experimental Cell Research

DOI:https://doi.org/10.1016/J.YEXCR.2021.112516· OSTI ID:23195347

Ko, Hyun Ju ^[1]; Kim, Jeongtae ^[2]; Ahn, Meejung ^[3]; Kim, Jin Hwa; Lee, Geun Soo ^[4]; Shin, Taekyun ^[1]

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1. Department of Veterinary Anatomy, College of Veterinary Medicine and Veterinary Medical Research Institute, Jeju National University, Jeju, 63243 (Korea, Republic of)
2. Department of Anatomy, Kosin University College of Medicine, Busan, 49267 (Korea, Republic of)
3. Department of Animal Science, College of Life Science, Sangji University, Wonju, 26339 (Korea, Republic of)
4. Skin science research team, Creation & Innovation research institute, It's hanbul Co., LTD., Gangnam-gu, Seoul, 06101 (Korea, Republic of)

Highlights: • EGT activated Nrf2/HO-1 pathway and HSP70 in UVB-irradiated keratinocytes. • EGT alleviated ROS production, apoptosis, and inflammation in UVB-irradiated keratinocytes. • EGT suppressed senescence and collagen imbalance in fibroblasts by inhibiting the keratinocyte-secreted factors. • EGT suppresses photoaging by UVB irradiation in a keratinocyte/fibroblast co-culture system. Ultraviolet B (UVB) irradiation induces skin damage and photoaging through several deleterious effects, including generation of reactive oxygen species (ROS), apoptosis of epidermal cells, inflammation, and collagen degradation in fibroblasts. Ergothioneine (EGT) is a naturally occurring amino acid with potential biological properties. We evaluated whether EGT protects against UVB-induced photoaging using a keratinocyte/fibroblast co-culture system. Keratinocytes were pretreated with EGT, irradiated with UVB, and co-cultured with fibroblasts. In keratinocytes, ROS production and apoptosis were assessed. We also analyzed the Nrf2/HO-1 pathway, HSP70, proapoptotic proteins, and paracrine cytokines by Western blotting and real-time PCR. Collagen degradation-related genes and senescence were also assessed in fibroblasts. EGT pretreatment of keratinocytes significantly inhibited downregulation of the Nrf2/HO-1 pathway and HSP70, and protected keratinocytes by suppressing production of ROS and cleavage of proapoptotic proteins, including caspase-8 and PARP. Furthermore, EGT significantly reduced the paracrine cytokines, including IL-1β, IL-6, and TNF-α. In co-cultures of fibroblasts with EGT-treated keratinocytes, the expression levels of collagen degradation-related genes and fibroblast senescence were significantly decreased; however, synthesis of procollagen type I was significantly increased. Our results confirm that EGT suppresses the modification of collagen homeostasis in fibroblasts by preventing downregulation of the Nrf2/HO-1 pathway and HSP70 in keratinocytes following UVB irradiation.

• OSTI ID: 23195347
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 1 Vol. 400; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
AMINO ACIDS
APOPTOSIS
CLEAVAGE
COLLAGEN
FIBROBLASTS
FORMATION DAMAGE
GENES
HOMEOSTASIS
INFLAMMATION
IRRADIATION
LYMPHOKINES
POLYMERASE CHAIN REACTION