Possible Involvement of Dermal Fibroblasts in Modulating Nrf2 Signaling in Epidermal Keratinocytes

Epidermal keratinocytes protect themselves by cooperating with neighboring cells against internal and external stresses, which leads not only to the maintenance of cell homeostasis but also to the prevention of skin aging. Although it is known that nuclear factor (NF)-E2-related factor 2 (Nrf2) sign...

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Bibliographic Details
Published in:Biological & pharmaceutical bulletin 2023/05/01, Vol.46(5), pp.725-729
Main Authors: Tsuruta, Yoshinobu, Katsuyama, Yushi, Okano, Yuri, Ozawa, Toshiyuki, Yoshimoto, Satoshi, Ando, Hideya, Masaki, Hitoshi, Ichihashi, Masamitsu
Format: Article
Language:English
Subjects:
Cell culture
Cooperation
Cytoplasm
Epidermis - metabolism
Fibroblasts
Fibroblasts - metabolism
Glutathione
Heme
Heme oxygenase (decyclizing)
Homeostasis
Humans
Inflammation
inflammatory response
intracellular antioxidant system
Keratinocytes
Keratinocytes - metabolism
Localization
NF-E2-Related Factor 2 - metabolism
NRF2 protein
nuclear factor (NF)-E2-related factor 2
Oxidative Stress
Oxygenase
Prostaglandin E2
Skin
Skin - metabolism
Ultraviolet Rays
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Summary:Epidermal keratinocytes protect themselves by cooperating with neighboring cells against internal and external stresses, which leads not only to the maintenance of cell homeostasis but also to the prevention of skin aging. Although it is known that nuclear factor (NF)-E2-related factor 2 (Nrf2) signaling plays a pivotal role in ameliorating oxidative stress and inflammatory responses under stress situations, it is unclear whether Nrf2 signaling in keratinocytes cooperates with neighboring cells such as dermal fibroblasts. Thus, this study was conducted to examine the influence of dermal fibroblasts on Nrf2 signaling in epidermal keratinocytes using a co-culture system. The results show that expression levels of Nrf2-regulated antioxidant factors, such as glutathione and heme oxygenase-1, in HaCaT keratinocytes (HaCaT KCs) are up-regulated in the presence of normal human dermal fibroblasts (NHDFs). In addition, the secretion of pro-inflammatory molecules, including interleukin-1α (IL-1α) and prostaglandin E2 (PGE2), is suppressed in co-cultures of NHDFs and UVB-irradiated HaCaT KCs. Interestingly, the localization of Nrf2 protein in HaCaT KCs was immediately translocated from the cytoplasm to the nucleus after the co-culture with NHDFs. These results suggest the possibility that Nrf2 signaling in keratinocytes is regulated in cooperation with dermal fibroblasts.
ISSN:0918-6158
1347-5215
DOI:10.1248/bpb.b22-00673