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

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, media...

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Main Authors: Peng Wu, Yongqian Cao, Ran Zhao, Yibing Wang
Format: Article
Language:English
Published: Taylor & Francis Group 2019-12-01
Series:Artificial Cells, Nanomedicine, and Biotechnology
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/21691401.2019.1593849
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author Peng Wu
Yongqian Cao
Ran Zhao
Yibing Wang
author_facet Peng Wu
Yongqian Cao
Ran Zhao
Yibing Wang
author_sort Peng Wu
collection DOAJ
description 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.
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spelling doaj.art-bedb5f8948464fc18cc30097ed7ed6f32022-12-22T03:02:09ZengTaylor & Francis GroupArtificial Cells, Nanomedicine, and Biotechnology2169-14012169-141X2019-12-014711416142210.1080/21691401.2019.1593849Netrin-1 plays a critical role in regulating capacities of epidermal stem cells upon ultraviolet-B (UV-B) irradiationPeng Wu0Yongqian Cao1Ran Zhao2Yibing Wang3Department of Burns and Plastic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, ChinaDepartment of Burns and Plastic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, ChinaDepartment of Burns and Plastic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, ChinaDepartment of Burns and Plastic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, ChinaLoss 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.https://www.tandfonline.com/doi/10.1080/21691401.2019.1593849Epidermal stem cellsskinultraviolet-Bnetrin-1Wnt/β-catenin
spellingShingle Peng Wu
Yongqian Cao
Ran Zhao
Yibing Wang
Netrin-1 plays a critical role in regulating capacities of epidermal stem cells upon ultraviolet-B (UV-B) irradiation
Artificial Cells, Nanomedicine, and Biotechnology
Epidermal stem cells
skin
ultraviolet-B
netrin-1
Wnt/β-catenin
title Netrin-1 plays a critical role in regulating capacities of epidermal stem cells upon ultraviolet-B (UV-B) irradiation
title_full Netrin-1 plays a critical role in regulating capacities of epidermal stem cells upon ultraviolet-B (UV-B) irradiation
title_fullStr Netrin-1 plays a critical role in regulating capacities of epidermal stem cells upon ultraviolet-B (UV-B) irradiation
title_full_unstemmed Netrin-1 plays a critical role in regulating capacities of epidermal stem cells upon ultraviolet-B (UV-B) irradiation
title_short Netrin-1 plays a critical role in regulating capacities of epidermal stem cells upon ultraviolet-B (UV-B) irradiation
title_sort netrin 1 plays a critical role in regulating capacities of epidermal stem cells upon ultraviolet b uv b irradiation
topic Epidermal stem cells
skin
ultraviolet-B
netrin-1
Wnt/β-catenin
url https://www.tandfonline.com/doi/10.1080/21691401.2019.1593849
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