11,12 Epoxyeicosatrienoic Acid Rescues Deteriorated Wound Healing in Diabetes

Epoxyeicosatrienoic acids (EET) facilitate regeneration in different tissues, and their benefit in dermal wound healing has been proven under normal conditions. In this study, we investigated the effect of 11,12 EET on dermal wound healing in diabetes. We induced diabetes by i.p. injection of strept...

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Autores principales:	Katharina Sommer, Heike Jakob, Caroline Reiche, Dirk Henrich, Jasmina Sterz, Johannes Frank, Ingo Marzi, Anna Lena Sander
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	wound repair diabetes EET neovascularization proliferation inflammatory reaction Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/98ef593b1dae454fa8dcc0dfd73d58bd
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spelling	oai:doaj.org-article:98ef593b1dae454fa8dcc0dfd73d58bd2021-11-11T17:07:49Z11,12 Epoxyeicosatrienoic Acid Rescues Deteriorated Wound Healing in Diabetes10.3390/ijms2221116641422-00671661-6596https://doaj.org/article/98ef593b1dae454fa8dcc0dfd73d58bd2021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11664https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Epoxyeicosatrienoic acids (EET) facilitate regeneration in different tissues, and their benefit in dermal wound healing has been proven under normal conditions. In this study, we investigated the effect of 11,12 EET on dermal wound healing in diabetes. We induced diabetes by i.p. injection of streptozotocin 2 weeks prior to wound creation on the dorsal side of the mouse ear. 11,12 EET was applied every second day on the wound, whereas the control groups received only solvent. Epithelialization was monitored every second day <i>intravitally</i> up to wound closure. Wounds were stained for VEGF, CD31, TGF-β, TNF-α, SDF-1α, NF-κB, and Ki-67, and fibroblasts were counted after hematoxylin-eosin stain on days 3, 6, 9, and 16 after wounding. After induction of diabetes, wounds closed on day 13.00 ± 2.20 standard deviation (SD). Local 11,12 ETT application improved wound closure significantly to day 8.40 ± 1.39 SD. EET treatment enhanced VEGF and CD31 expression in wounds on day 3. It also seemed to raise TNF-α level on all days investigated as well as TGF-β level on days 3 and 6. A decrease in NF-κB could be observed on days 9 and 16 after EET application. The latter findings were not significant. SDF-1α expression was not influenced by EET application, and Ki-67 was significantly less in the EET group on day 9 after EET application. The number of fibroblasts was significantly increased on day 9 after the 11,12 EET application. 11,12 EET improve deteriorated wound healing in diabetes by enhancing neoangiogenesis, especially in the early phase of wound healing. Furthermore, they contribute to the dissolution of the initial inflammatory reaction, allowing the crucial transition from the inflammatory to proliferative phase in wound healing.Katharina SommerHeike JakobCaroline ReicheDirk HenrichJasmina SterzJohannes FrankIngo MarziAnna Lena SanderMDPI AGarticlewound repairdiabetesEETneovascularizationproliferationinflammatory reactionBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11664, p 11664 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	wound repair diabetes EET neovascularization proliferation inflammatory reaction Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	wound repair diabetes EET neovascularization proliferation inflammatory reaction Biology (General) QH301-705.5 Chemistry QD1-999 Katharina Sommer Heike Jakob Caroline Reiche Dirk Henrich Jasmina Sterz Johannes Frank Ingo Marzi Anna Lena Sander 11,12 Epoxyeicosatrienoic Acid Rescues Deteriorated Wound Healing in Diabetes
description	Epoxyeicosatrienoic acids (EET) facilitate regeneration in different tissues, and their benefit in dermal wound healing has been proven under normal conditions. In this study, we investigated the effect of 11,12 EET on dermal wound healing in diabetes. We induced diabetes by i.p. injection of streptozotocin 2 weeks prior to wound creation on the dorsal side of the mouse ear. 11,12 EET was applied every second day on the wound, whereas the control groups received only solvent. Epithelialization was monitored every second day <i>intravitally</i> up to wound closure. Wounds were stained for VEGF, CD31, TGF-β, TNF-α, SDF-1α, NF-κB, and Ki-67, and fibroblasts were counted after hematoxylin-eosin stain on days 3, 6, 9, and 16 after wounding. After induction of diabetes, wounds closed on day 13.00 ± 2.20 standard deviation (SD). Local 11,12 ETT application improved wound closure significantly to day 8.40 ± 1.39 SD. EET treatment enhanced VEGF and CD31 expression in wounds on day 3. It also seemed to raise TNF-α level on all days investigated as well as TGF-β level on days 3 and 6. A decrease in NF-κB could be observed on days 9 and 16 after EET application. The latter findings were not significant. SDF-1α expression was not influenced by EET application, and Ki-67 was significantly less in the EET group on day 9 after EET application. The number of fibroblasts was significantly increased on day 9 after the 11,12 EET application. 11,12 EET improve deteriorated wound healing in diabetes by enhancing neoangiogenesis, especially in the early phase of wound healing. Furthermore, they contribute to the dissolution of the initial inflammatory reaction, allowing the crucial transition from the inflammatory to proliferative phase in wound healing.
format	article
author	Katharina Sommer Heike Jakob Caroline Reiche Dirk Henrich Jasmina Sterz Johannes Frank Ingo Marzi Anna Lena Sander
author_facet	Katharina Sommer Heike Jakob Caroline Reiche Dirk Henrich Jasmina Sterz Johannes Frank Ingo Marzi Anna Lena Sander
author_sort	Katharina Sommer
title	11,12 Epoxyeicosatrienoic Acid Rescues Deteriorated Wound Healing in Diabetes
title_short	11,12 Epoxyeicosatrienoic Acid Rescues Deteriorated Wound Healing in Diabetes
title_full	11,12 Epoxyeicosatrienoic Acid Rescues Deteriorated Wound Healing in Diabetes
title_fullStr	11,12 Epoxyeicosatrienoic Acid Rescues Deteriorated Wound Healing in Diabetes
title_full_unstemmed	11,12 Epoxyeicosatrienoic Acid Rescues Deteriorated Wound Healing in Diabetes
title_sort	11,12 epoxyeicosatrienoic acid rescues deteriorated wound healing in diabetes
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/98ef593b1dae454fa8dcc0dfd73d58bd
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11,12 Epoxyeicosatrienoic Acid Rescues Deteriorated Wound Healing in Diabetes

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