Universität zu Köln

Riese, Anna, Eilert, Yvonne, Meyer, Yvonne, Arin, Meral, Baron, Jens M., Eming, Sabine, Krieg, Thomas and Kurschat, Peter (2012). Epidermal Expression of Neuropilin 1 Protects Murine keratinocytes from UVB-induced apoptosis. PLoS One, 7 (12). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1932-6203

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Abstract

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Riese, Anna UNSPECIFIED UNSPECIFIED UNSPECIFIED Eilert, Yvonne UNSPECIFIED UNSPECIFIED UNSPECIFIED Meyer, Yvonne UNSPECIFIED UNSPECIFIED UNSPECIFIED Arin, Meral UNSPECIFIED UNSPECIFIED UNSPECIFIED Baron, Jens M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Eming, Sabine UNSPECIFIED UNSPECIFIED UNSPECIFIED Krieg, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Kurschat, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-476802
DOI:	10.1371/journal.pone.0050944
Journal or Publication Title:	PLoS One
Volume:	7
Number:	12
Date:	2012
Publisher:	PUBLIC LIBRARY SCIENCE
Place of Publication:	SAN FRANCISCO
ISSN:	1932-6203
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ENDOTHELIAL GROWTH-FACTOR; AUTOCRINE SURVIVAL FACTOR; TUMOR-CELLS; SKIN-CANCER; SEMAPHORIN; INITIATION; CARCINOMA; RECEPTOR; DIFFERENTIATION; PATHWAY Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/47680