Keratinocyte Growth Factor 2 Ameliorates UVB-Induced Skin Damage via Activating the AhR/Nrf2 Signaling Pathway

Abstract

Objective: Exposure to ultraviolet B (UVB) can cause skin damage through oxidative stress, DNA damage, and apoptosis. Keratinocyte growth factor (KGF) has been shown to reduce the content of intracellular reactive oxygen species (ROS) following UVB exposure, a role that is crucial for the efficient photoprotection of skin. The present study evaluated the photoprotective effect of KGF-2 on UVB-induced skin damage and explored its potential molecular mechanism.Methods: To evaluate the effect of KGF-2 on UVB-induced damage ex vivo, a human epidermal full-thickness skin equivalent was pretreated without or with KGF-2 and then exposed to UVB and the levels of histopathological changes, DNA damage, inflammation, and apoptosis were then evaluated. The ability of KGF-2 to protect the cells against UVB-inflicted damage and its effect on ROS production, apoptosis, and mitochondrial dysfunction were determined in HaCaT cells.Results: Pretreatment of the epidermis with KGF-2 ameliorated the extent of photodamage. At the cellular level, KGF-2 could attenuate ROS production, apoptosis, DNA damage, and mitochondrial dysfunction caused by UVB exposure. KGF-2 could also activate the aryl hydrocarbon receptor (AhR) to trigger the Nrf2 signaling pathway.Conclusion: Taken together, our findings suggested that KGF-2 could ameliorate UVB-induced skin damage through inhibiting apoptosis, reducing oxidative stress, and preventing DNA damage and mitochondrial dysfunction via regulating AhR/Nrf2 signaling pathway.

Photoaging and Sequential Function Reversal with Cellular-Resolution Optical Coherence Tomography in a Nude Mice Model

“…This is a corollary of the keratinocyte-fibroblast interactions in wound healing and barrier functions [30]. Fibroblasts promote epidermal thickening to ameliorate UVB-induced skin damage by inducing the keratinocyte growth factor (KGF) [31,32]. The epidermis also thickens in the UVA-irradiated mice, mediated by the KGF and the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway [33][34][35].…”

The Aryl Hydrocarbon Receptor in the Pathogenesis of Environmentally-Induced Squamous Cell Carcinomas of the Skin

“…These data indicate that by repressing the repair of UVB radiation-induced DNA photoproducts, AHR may critically contribute to skin photocarcinogenesis. Recently, this concept was challenged by a study reporting that an activation of AHR signaling by keratinocyte growth factor-2 (KGF2) stimulates CPD clearance as early as one hour after UVB exposure ( 127 ). However, it is not clear whether this effect depended on alterations in NER activity or apoptosis.…”

Cryptotanshinone protects skin cells from ultraviolet radiation-induced photoaging via its antioxidant effect and by reducing mitochondrial dysfunction and inhibiting apoptosis

“…After that, the PBS was replaced with fresh medium containing no CTS or the corresponding concentrations of CTS followed by 2 h of incubation. An immunofluorescence staining assay was performed as described in our previous study ( Gao et al, 2021 ). HaCaT cells were incubated with anti-γ-H2AX (#9718, 1: 1000, Cell Signaling Technology, Beverly, MA, United States) and anti-CPD (CAC-NM-DND-001, 1: 1000, Cosmo Bio, Tokyo, Japan) at 4°C overnight.…”

“…Cytoplasmic and nuclear proteins were extracted from the cells using NE-PER ™ Reagents (Thermo scientific, NY, United States). Total proteins, cytoplasmic proteins and nuclear proteins were then subjected to western blot performed as described in our previous study (Gao et al, 2021). The blot was incubated with primary antibody against caspase-3 (19677-1-AP, 1: 1,000, Proteintech, Wuhan, China), caspase-9 (66169-1-Ig, 1: 1,000, Proteintech, Wuhan, China), peroxisome proliferator-activated receptor-γ co-activator-1α (PGC-1α) (66369-1-Ig, 1: 1,000, Proteintech, Wuhan, China), Nrf2 (66504-1-Ig, 1: 1,000, Proteintech,…”