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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Taylor & Francis Group
2019-12-01
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Series: | Artificial Cells, Nanomedicine, and Biotechnology |
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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. |
first_indexed | 2024-04-13T04:36:14Z |
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institution | Directory Open Access Journal |
issn | 2169-1401 2169-141X |
language | English |
last_indexed | 2024-04-13T04:36:14Z |
publishDate | 2019-12-01 |
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series | Artificial Cells, Nanomedicine, and Biotechnology |
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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