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Research Article

Netrin-1 plays a critical role in regulating capacities of epidermal stem cells upon ultraviolet-B (UV-B) irradiation

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Pages 1416-1422 | Received 27 Oct 2018, Accepted 08 Dec 2018, Published online: 23 Apr 2019
 

Abstract

Loss of the capacities of epidermal stem cells (ESCs) induced by ultraviolet-B (UV-B) irradiation has been widely associated with various skin diseases. Netrin-1, a member of the axonal guidance protein family, has displayed diverse biological functions in different types of cells and tissues, mediated by its specific receptor UNC-5 homolog B (UNC5b). In this study, we examined the physiological functions of netrin-1 and UNC5b in ESCs upon UV-B exposure. Our results indicate that UNC5b is expressed in ESCs, and its expression is upregulated in response to UV-B radiation. We found that treatment with netrin-1 prevented UV-B radiation-induced oxidative stress by reducing the generation of reactive oxygen species (ROS) and expression of NADPH oxidase 4 (NOX-4). Additionally, treatment with netrin-1 improved UV-B radiation-induced mitochondrial dysfunction by increasing mitochondrial membrane potential (MMP) levels and adenosine triphosphate (ATP) production. The presence of netrin-1 attenuated UV-B radiation-induced lactic dehydrogenase (LDH) release. UV-B exposure resulted in the loss of the capacities of ESCs by reducing the expressions of integrin β1 and Krt19, the two major ESC markers. Importantly, this process was prevented by netrin-1. Silencing of UNC5b abolished the effects of netrin-1 on the expression of integrin β1 and Krt19, suggesting that the effects of netrin-1 in maintaining the capacities of ESCs are dependent on UNC5b. Mechanistically, we found that the Wnt/β-catenin signalling may be involved. Our findings suggest that netrin-1 may serve as a therapeutic agent for the treatment of skin diseases.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

National Natural Science Foundation of China [No.81571911, 81201471 and 81171818]; Science and Technology Development Program of Shandong Province [No.2015GSF118008].