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

Shuang Gao,Xuenan Li,Xiaokun Li,Keke Guo,Lusheng Wang,Yu Chen,Nuo Xu,Jungang Zhao,Zhenlin Hu,Rongrong Jing

doi:10.3389/fphar.2021.655281

Shuang Gao, Xuenan Li + Show 8 more

Open Access

https://doi.org/10.3389/fphar.2021.655281

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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.

Highlights

The skin, the largest organ of the human body, is divided into three different layers, called subcutis, dermis, and epidermis
Human epidermal equivalent (HEE) irradiated with 200 mJ/cm2 dose of UVB followed by 24 h of culturing revealed a significant increase in the number of UVBdamaged keratinocyte compared with control HEE, but the number of UVB-damaged keratinocyte was reduced when HEE was pretreated with KFG-2 before UVB irradiation (Figure 1A)
Consistent with the result obtained from HE staining, the result obtained from TUNEL assay showed that Keratinocyte growth factor (KGF)-2 could prevent the keratinocytes from undergoing apoptosis in the UVB-irradiated HEE (Figure 1B)

Summary

Introduction

The skin, the largest organ of the human body, is divided into three different layers, called subcutis, dermis, and epidermis. The outermost epidermis is mainly composed of keratinocytes and it provides a selective physical barrier to protect human beings from harmful substances that come from the environment (Eckhart and Zeeuwen 2018). UV is composed of three different types classified by wavelengths: UVA (320–400 nm), UVB (280–320 nm), and UVC. UVC is effectively blocked from reaching the Earth’s surface by the ozone layer of the atmosphere. UVA can penetrate deeply into the dermis to cause aging and wrinkling of the skin. UVB on the other hand is regarded as “burning rays” and it is almost completely absorbed by the epidermis, where it can induce oxidative damage, inflammation, DNA damage, photoaging, and apoptosis (Tomaino et al, 2006; Oh et al, 2016; D’Orazio et al, 2013; de Gruijl 2000)

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