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Epidermal Expression of Neuropilin 1 Protects Murine keratinocytes from UVB-induced apoptosis

BACKGROUND: Neuropilin 1 (NRP1) is expressed on several cell types including neurons and endothelial cells, where it functions as an important regulator in development and during angiogenesis. As a cell surface receptor, NRP1 is able to bind to members of the VEGF family of growth factors and to sec...

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Autores principales: Riese, Anna, Eilert, Yvonne, Meyer, Yvonne, Arin, Meral, Baron, Jens M., Eming, Sabine, Krieg, Thomas, Kurschat, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3518474/
https://www.ncbi.nlm.nih.gov/pubmed/23251405
http://dx.doi.org/10.1371/journal.pone.0050944
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author Riese, Anna
Eilert, Yvonne
Meyer, Yvonne
Arin, Meral
Baron, Jens M.
Eming, Sabine
Krieg, Thomas
Kurschat, Peter
author_facet Riese, Anna
Eilert, Yvonne
Meyer, Yvonne
Arin, Meral
Baron, Jens M.
Eming, Sabine
Krieg, Thomas
Kurschat, Peter
author_sort Riese, Anna
collection PubMed
description BACKGROUND: Neuropilin 1 (NRP1) is expressed on several cell types including neurons and endothelial cells, where it functions as an important regulator in development and during angiogenesis. As a cell surface receptor, NRP1 is able to bind to members of the VEGF family of growth factors and to secreted class 3 semaphorins. Neuropilin 1 is also highly expressed in keratinocytes, but the function of NRP1 in epidermal physiology and pathology is still unclear. METHODS AND RESULTS: To elucidate the role of NRP1 in skin in vivo we generated an epidermis-specific neuropilin 1 knock out mouse model by using the Cre-LoxP-System. Mice were viable and fertile and did not display any obvious skin or hair defects. After challenge with UVB irradiation, we found that deletion of epidermal NRP1 leads to increased rates of apoptosis both in vitro and in vivo. NRP1-deficient primary keratinocytes cultured in vitro showed significantly higher rates of apoptosis 24 hours after UVB. Likewise, there is a significant increase of active caspase 3 positive cells in the epidermis of Keratin 14-Cre-NRP1 (−/−) mice 24 hours after UVB irradiation. By Western Blot analysis we could show that NRP1 influences the cytosolic levels of Bcl-2, a pro-survival member of the Bcl-2 family. After UVB irradiation the amounts of Bcl-2 decrease in both protein extracts from murine epidermis and in NRP1-deficient keratinocytes in vitro, whereas wild type cells retain their Bcl-2 levels. Likewise, levels of phospho-Erk and Rac1 were lower in NRP1-knock out keratinocytes, whereas levels of pro-apoptotic p53 were higher. CONCLUSION: NRP1 expression in keratinocytes is dispensable for normal skin development. Upon UVB challenge, NRP1 contributes to the prevention of keratinocyte apoptosis. This pro-survival function of NRP1 is accompanied by the maintenance of high levels of the antiapoptotic regulator Bcl-2 and by lower levels of pro-apoptotic p53.
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spelling pubmed-35184742012-12-18 Epidermal Expression of Neuropilin 1 Protects Murine keratinocytes from UVB-induced apoptosis Riese, Anna Eilert, Yvonne Meyer, Yvonne Arin, Meral Baron, Jens M. Eming, Sabine Krieg, Thomas Kurschat, Peter PLoS One Research Article BACKGROUND: Neuropilin 1 (NRP1) is expressed on several cell types including neurons and endothelial cells, where it functions as an important regulator in development and during angiogenesis. As a cell surface receptor, NRP1 is able to bind to members of the VEGF family of growth factors and to secreted class 3 semaphorins. Neuropilin 1 is also highly expressed in keratinocytes, but the function of NRP1 in epidermal physiology and pathology is still unclear. METHODS AND RESULTS: To elucidate the role of NRP1 in skin in vivo we generated an epidermis-specific neuropilin 1 knock out mouse model by using the Cre-LoxP-System. Mice were viable and fertile and did not display any obvious skin or hair defects. After challenge with UVB irradiation, we found that deletion of epidermal NRP1 leads to increased rates of apoptosis both in vitro and in vivo. NRP1-deficient primary keratinocytes cultured in vitro showed significantly higher rates of apoptosis 24 hours after UVB. Likewise, there is a significant increase of active caspase 3 positive cells in the epidermis of Keratin 14-Cre-NRP1 (−/−) mice 24 hours after UVB irradiation. By Western Blot analysis we could show that NRP1 influences the cytosolic levels of Bcl-2, a pro-survival member of the Bcl-2 family. After UVB irradiation the amounts of Bcl-2 decrease in both protein extracts from murine epidermis and in NRP1-deficient keratinocytes in vitro, whereas wild type cells retain their Bcl-2 levels. Likewise, levels of phospho-Erk and Rac1 were lower in NRP1-knock out keratinocytes, whereas levels of pro-apoptotic p53 were higher. CONCLUSION: NRP1 expression in keratinocytes is dispensable for normal skin development. Upon UVB challenge, NRP1 contributes to the prevention of keratinocyte apoptosis. This pro-survival function of NRP1 is accompanied by the maintenance of high levels of the antiapoptotic regulator Bcl-2 and by lower levels of pro-apoptotic p53. Public Library of Science 2012-12-10 /pmc/articles/PMC3518474/ /pubmed/23251405 http://dx.doi.org/10.1371/journal.pone.0050944 Text en © 2012 Riese et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Riese, Anna
Eilert, Yvonne
Meyer, Yvonne
Arin, Meral
Baron, Jens M.
Eming, Sabine
Krieg, Thomas
Kurschat, Peter
Epidermal Expression of Neuropilin 1 Protects Murine keratinocytes from UVB-induced apoptosis
title Epidermal Expression of Neuropilin 1 Protects Murine keratinocytes from UVB-induced apoptosis
title_full Epidermal Expression of Neuropilin 1 Protects Murine keratinocytes from UVB-induced apoptosis
title_fullStr Epidermal Expression of Neuropilin 1 Protects Murine keratinocytes from UVB-induced apoptosis
title_full_unstemmed Epidermal Expression of Neuropilin 1 Protects Murine keratinocytes from UVB-induced apoptosis
title_short Epidermal Expression of Neuropilin 1 Protects Murine keratinocytes from UVB-induced apoptosis
title_sort epidermal expression of neuropilin 1 protects murine keratinocytes from uvb-induced apoptosis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3518474/
https://www.ncbi.nlm.nih.gov/pubmed/23251405
http://dx.doi.org/10.1371/journal.pone.0050944
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