Skin regeneration with conical and hair follicle structure of deep second-degree scalding injuries via combined expression of the EPO receptor and beta common receptor by local subcutaneous injection of nanosized rhEPO

Augustinus Bader1, Sabine Ebert1, Shibashish Giri1, Mathias Kremer2, Shuhua Liu2, Andreas Nerlich5, Christina I Günter³, Dagmar U Smith4, Hans-Günther Machens2,31Department of Applied Stem Cell Biology and Cell Techniques, Centre for Biotechnology and Biomedici...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Ebert S, Bader A, Liu S, Kremer M, Giri S, Machens HG, Nerlich A, Günter CI, Smith DU
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2012
Materias:
Acceso en línea:https://doaj.org/article/05944f87ef50460b8274842d08bf5ddf
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:05944f87ef50460b8274842d08bf5ddf
record_format dspace
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Ebert S
Bader A
Liu S
Kremer M
Giri S
Machens HG
Nerlich A
Günter CI
Smith DU
Skin regeneration with conical and hair follicle structure of deep second-degree scalding injuries via combined expression of the EPO receptor and beta common receptor by local subcutaneous injection of nanosized rhEPO
description Augustinus Bader1, Sabine Ebert1, Shibashish Giri1, Mathias Kremer2, Shuhua Liu2, Andreas Nerlich5, Christina I Günter³, Dagmar U Smith4, Hans-Günther Machens2,31Department of Applied Stem Cell Biology and Cell Techniques, Centre for Biotechnology and Biomedicine, University of Leipzig, Leipzieg, 2Department of Plastic and Hand Surgery, University of Lübeck, Lübeck, 3Department of Plastic and Hand Surgery, Technische Universität München, Munich, 4Münchner Studienzentrum, Technische Universität München, Munich, 5Institute of Pathology, Klinikum München-Bogenhausen, Munich, GermanyBackground: Acceleration of skin regeneration is still an unsolved problem in the clinical treatment of patients suffering from deep burns and scalds. Although erythropoietin (EPO) has a protective role in a wide range of organs and cells during ischemia and after trauma, it has been recently discovered that EPO is not tissue-protective in the common β subunit receptor (βCR) knockout mouse. The protective capacity of EPO in tissue is mediated via a heteroreceptor complex comprising both the erythropoietin receptor (EPOR) and βCR. However, proof of coexpression of these heterogenic receptors in regenerating skin after burns is still lacking.Methods: To understand the role of nanosized recombinant human erythropoietin (rhEPO) in wound healing, we investigated the effects of subcutaneous injections of EPO on skin regeneration after deep second-degree scalding injuries. Our aim was to determine if joint expression of EPOR and βCR is a prerequisite for the tissue-protective effect of rhEPO. The efficiency in wound regeneration in a skin scalding injury mouse model was examined. A deep second-degree dermal scald injury was produced on the backs of 20 female Balb/c mice which were subsequently randomized to four experimental groups, two of which received daily subcutaneous injections of rhEPO. At days 7 and 14, the mice were sacrificed and the effects of rhEPO were analyzed with respect to grade of re-epithelialization (wound closure) and stage of epidermal maturation. This was investigated using different histological parameters of epithelial covering, such as depth of the epidermal layer, epidermal stratification, and presence of conical and hair follicle structures.Results: Expression of EPOR, βCR, and growth hormone receptor at the mRNA and protein levels was demonstrated with reverse transcriptase polymerase chain reaction and Western blot analysis. After rhEPO treatment, the rate of re-epithelialization of the scalding injury was increased and the time to final wound closure was reduced. In addition, the quality of regenerated skin was improved. In this investigation, for the first time, we demonstrated coexpression of EPOR and βCR at the RNA and protein levels in vivo using a deep second-degree scalding injury mouse model. These results highlight the potential role of rhEPO in the improved treatment of burns patients, which might be crucial for the development of innovative new therapy regimes.Conclusion: Local injection of nanosized rhEPO directly to the injury site rather than systemic administration for deep second-degree scalding injuries achieved complete skin regeneration with conical and hair follicle structure via combined expression of EPOR and βCR.Keywords: burns, nanosize, common β subunit, erythropoietin, receptor, local injection
format article
author Ebert S
Bader A
Liu S
Kremer M
Giri S
Machens HG
Nerlich A
Günter CI
Smith DU
author_facet Ebert S
Bader A
Liu S
Kremer M
Giri S
Machens HG
Nerlich A
Günter CI
Smith DU
author_sort Ebert S
title Skin regeneration with conical and hair follicle structure of deep second-degree scalding injuries via combined expression of the EPO receptor and beta common receptor by local subcutaneous injection of nanosized rhEPO
title_short Skin regeneration with conical and hair follicle structure of deep second-degree scalding injuries via combined expression of the EPO receptor and beta common receptor by local subcutaneous injection of nanosized rhEPO
title_full Skin regeneration with conical and hair follicle structure of deep second-degree scalding injuries via combined expression of the EPO receptor and beta common receptor by local subcutaneous injection of nanosized rhEPO
title_fullStr Skin regeneration with conical and hair follicle structure of deep second-degree scalding injuries via combined expression of the EPO receptor and beta common receptor by local subcutaneous injection of nanosized rhEPO
title_full_unstemmed Skin regeneration with conical and hair follicle structure of deep second-degree scalding injuries via combined expression of the EPO receptor and beta common receptor by local subcutaneous injection of nanosized rhEPO
title_sort skin regeneration with conical and hair follicle structure of deep second-degree scalding injuries via combined expression of the epo receptor and beta common receptor by local subcutaneous injection of nanosized rhepo
publisher Dove Medical Press
publishDate 2012
url https://doaj.org/article/05944f87ef50460b8274842d08bf5ddf
work_keys_str_mv AT eberts skinregenerationwithconicalandhairfolliclestructureofdeepseconddegreescaldinginjuriesviacombinedexpressionoftheeporeceptorandbetacommonreceptorbylocalsubcutaneousinjectionofnanosizedrhepo
AT badera skinregenerationwithconicalandhairfolliclestructureofdeepseconddegreescaldinginjuriesviacombinedexpressionoftheeporeceptorandbetacommonreceptorbylocalsubcutaneousinjectionofnanosizedrhepo
AT lius skinregenerationwithconicalandhairfolliclestructureofdeepseconddegreescaldinginjuriesviacombinedexpressionoftheeporeceptorandbetacommonreceptorbylocalsubcutaneousinjectionofnanosizedrhepo
AT kremerm skinregenerationwithconicalandhairfolliclestructureofdeepseconddegreescaldinginjuriesviacombinedexpressionoftheeporeceptorandbetacommonreceptorbylocalsubcutaneousinjectionofnanosizedrhepo
AT giris skinregenerationwithconicalandhairfolliclestructureofdeepseconddegreescaldinginjuriesviacombinedexpressionoftheeporeceptorandbetacommonreceptorbylocalsubcutaneousinjectionofnanosizedrhepo
AT machenshg skinregenerationwithconicalandhairfolliclestructureofdeepseconddegreescaldinginjuriesviacombinedexpressionoftheeporeceptorandbetacommonreceptorbylocalsubcutaneousinjectionofnanosizedrhepo
AT nerlicha skinregenerationwithconicalandhairfolliclestructureofdeepseconddegreescaldinginjuriesviacombinedexpressionoftheeporeceptorandbetacommonreceptorbylocalsubcutaneousinjectionofnanosizedrhepo
AT gampuumlnterci skinregenerationwithconicalandhairfolliclestructureofdeepseconddegreescaldinginjuriesviacombinedexpressionoftheeporeceptorandbetacommonreceptorbylocalsubcutaneousinjectionofnanosizedrhepo
AT smithdu skinregenerationwithconicalandhairfolliclestructureofdeepseconddegreescaldinginjuriesviacombinedexpressionoftheeporeceptorandbetacommonreceptorbylocalsubcutaneousinjectionofnanosizedrhepo
_version_ 1718403297318010880
spelling oai:doaj.org-article:05944f87ef50460b8274842d08bf5ddf2021-12-02T01:04:03ZSkin regeneration with conical and hair follicle structure of deep second-degree scalding injuries via combined expression of the EPO receptor and beta common receptor by local subcutaneous injection of nanosized rhEPO1176-91141178-2013https://doaj.org/article/05944f87ef50460b8274842d08bf5ddf2012-03-01T00:00:00Zhttp://www.dovepress.com/skin-regeneration-with-conical-and-hair-follicle-structure-of-deep-sec-a9422https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Augustinus Bader1, Sabine Ebert1, Shibashish Giri1, Mathias Kremer2, Shuhua Liu2, Andreas Nerlich5, Christina I Günter³, Dagmar U Smith4, Hans-Günther Machens2,31Department of Applied Stem Cell Biology and Cell Techniques, Centre for Biotechnology and Biomedicine, University of Leipzig, Leipzieg, 2Department of Plastic and Hand Surgery, University of Lübeck, Lübeck, 3Department of Plastic and Hand Surgery, Technische Universität München, Munich, 4Münchner Studienzentrum, Technische Universität München, Munich, 5Institute of Pathology, Klinikum München-Bogenhausen, Munich, GermanyBackground: Acceleration of skin regeneration is still an unsolved problem in the clinical treatment of patients suffering from deep burns and scalds. Although erythropoietin (EPO) has a protective role in a wide range of organs and cells during ischemia and after trauma, it has been recently discovered that EPO is not tissue-protective in the common β subunit receptor (βCR) knockout mouse. The protective capacity of EPO in tissue is mediated via a heteroreceptor complex comprising both the erythropoietin receptor (EPOR) and βCR. However, proof of coexpression of these heterogenic receptors in regenerating skin after burns is still lacking.Methods: To understand the role of nanosized recombinant human erythropoietin (rhEPO) in wound healing, we investigated the effects of subcutaneous injections of EPO on skin regeneration after deep second-degree scalding injuries. Our aim was to determine if joint expression of EPOR and βCR is a prerequisite for the tissue-protective effect of rhEPO. The efficiency in wound regeneration in a skin scalding injury mouse model was examined. A deep second-degree dermal scald injury was produced on the backs of 20 female Balb/c mice which were subsequently randomized to four experimental groups, two of which received daily subcutaneous injections of rhEPO. At days 7 and 14, the mice were sacrificed and the effects of rhEPO were analyzed with respect to grade of re-epithelialization (wound closure) and stage of epidermal maturation. This was investigated using different histological parameters of epithelial covering, such as depth of the epidermal layer, epidermal stratification, and presence of conical and hair follicle structures.Results: Expression of EPOR, βCR, and growth hormone receptor at the mRNA and protein levels was demonstrated with reverse transcriptase polymerase chain reaction and Western blot analysis. After rhEPO treatment, the rate of re-epithelialization of the scalding injury was increased and the time to final wound closure was reduced. In addition, the quality of regenerated skin was improved. In this investigation, for the first time, we demonstrated coexpression of EPOR and βCR at the RNA and protein levels in vivo using a deep second-degree scalding injury mouse model. These results highlight the potential role of rhEPO in the improved treatment of burns patients, which might be crucial for the development of innovative new therapy regimes.Conclusion: Local injection of nanosized rhEPO directly to the injury site rather than systemic administration for deep second-degree scalding injuries achieved complete skin regeneration with conical and hair follicle structure via combined expression of EPOR and βCR.Keywords: burns, nanosize, common β subunit, erythropoietin, receptor, local injectionEbert SBader ALiu SKremer MGiri SMachens HGNerlich AGünter CISmith DUDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2012, Iss default, Pp 1227-1237 (2012)