Abstract
Epidermal stem cells (ESCs) play essential roles in maintaining skin homeostasis and cell turnover of skin. Long-term exposure to UV-B irradiation induces a decrease in the population of ESCs and impairs the capacities of ESCs. The P2Y11 receptor (P2Y11R) is an important member of the P2 receptor family and plays a key role in mediating purinergic signaling and intracellular effects. In this study, we found that UV-B irradiation induced an increase in P2Y11R in ESCs. Antagonism of P2Y11R using NF157 ameliorated UV-B irradiation-induced oxidative stress by reducing reactive oxygen species (ROS) production and NADPH oxidase-4 (NOX-4) expression. Additionally, treatment with NF157 had a protective effect against UV-B irradiation-induced mitochondrial dysfunction by increasing mitochondrial membrane potential (MMP) and cytochrome c oxidase activity. Also, NF157 could mitigate lactate dehydrogenase (LDH) release and decreased the tumor necrosis factor-↑ (TNF-α), interleukin-6 (IL-6), and IL-8 secretion. Importantly, we found that treatment with NF157 attenuated UV-B irradiation-induced loss of ESCs capability by restoring the expression of integrin β1 and Krt19. Mechanistically, treatment with NF157 prevented UV-B irradiation-induced destruction of the Wnt/β-catenin signaling transduction pathway by increasing the expression of Wnt1, Wnt3a, c-Myc, and cyclin D1. These findings suggest a novel function of P2Y11R in regulating the capacities of ESCs upon UV-B irradiation.