Improved diabetic wound healing by LFcinB is associated with relevant changes in the skin immune response and microbiota
Bovine lactoferricin (LFcinB) has antimicrobial and immunomodulatory properties; however, the effects on diabetic wound healing remain poorly understood. The wound healing potential of LFcinB was investigated with in vitro, ex vivo, and in vivo models. Cell migration and proliferation were tested on...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-03-01
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| Series: | Molecular Therapy: Methods & Clinical Development |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2329050121000231 |
| _version_ | 1818667698131828736 |
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| author | Michelle V. Mouritzen Marija Petkovic Katrine Qvist Steen S. Poulsen Susana Alarico Ermelindo C. Leal Louise T. Dalgaard Nuno Empadinhas Eugenia Carvalho Håvard Jenssen |
| author_facet | Michelle V. Mouritzen Marija Petkovic Katrine Qvist Steen S. Poulsen Susana Alarico Ermelindo C. Leal Louise T. Dalgaard Nuno Empadinhas Eugenia Carvalho Håvard Jenssen |
| author_sort | Michelle V. Mouritzen |
| collection | DOAJ |
| description | Bovine lactoferricin (LFcinB) has antimicrobial and immunomodulatory properties; however, the effects on diabetic wound healing remain poorly understood. The wound healing potential of LFcinB was investigated with in vitro, ex vivo, and in vivo models. Cell migration and proliferation were tested on keratinocytes and on porcine ears. A type 1 diabetic mouse model was also used to evaluate wound healing kinetics, bacterial diversity patterns, and the effect of LFcinB on oxidative stress, macrophage phenotype, angiogenesis, and collagen deposition. LFcinB increased keratinocyte migration in vitro (p < 0.05) and ex vivo (p < 0.001) and improved wound healing in diabetic mice (p < 0.05), though not in normoglycemic control mice. In diabetic mouse wounds, LFcinB treatment led to the eradication of Bacillus pumilus, a decrease in Staphylococcus aureus, and an increase in the Staphylococcus xylosus prevalence. LFcinB increased angiogenesis in diabetic mice (p < 0.01), but this was decreased in control mice (p < 0.05). LFcinB improved collagen deposition in both diabetic and control mice (p < 0.05). Both oxidative stress and the M1-to-M2 macrophage ratios were decreased in LFcinB-treated wounds of diabetic animals (p < 0.001 and p < 0.05, respectively) compared with saline, suggesting a downregulation of inflammation in diabetic wounds. In conclusion, LFcinB treatment demonstrated noticeable positive effects on diabetic wound healing. |
| first_indexed | 2024-12-17T06:24:33Z |
| format | Article |
| id | doaj.art-ec54cc756c054ca4b2611f428ce5d18c |
| institution | Directory Open Access Journal |
| issn | 2329-0501 |
| language | English |
| last_indexed | 2024-12-17T06:24:33Z |
| publishDate | 2021-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Methods & Clinical Development |
| spelling | doaj.art-ec54cc756c054ca4b2611f428ce5d18c2022-12-21T22:00:20ZengElsevierMolecular Therapy: Methods & Clinical Development2329-05012021-03-0120726739Improved diabetic wound healing by LFcinB is associated with relevant changes in the skin immune response and microbiotaMichelle V. Mouritzen0Marija Petkovic1Katrine Qvist2Steen S. Poulsen3Susana Alarico4Ermelindo C. Leal5Louise T. Dalgaard6Nuno Empadinhas7Eugenia Carvalho8Håvard Jenssen9Department of Science and Environment, Roskilde University, Roskilde, DenmarkDepartment of Science and Environment, Roskilde University, Roskilde, Denmark; Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; Institute for Interdisciplinary Research, University of Coimbra, Coimbra, PortugalDepartment of Science and Environment, Roskilde University, Roskilde, DenmarkDepartment of Biomedical Science, University of Copenhagen, Copenhagen, DenmarkCenter for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; Institute for Interdisciplinary Research, University of Coimbra, Coimbra, PortugalCenter for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; Institute for Interdisciplinary Research, University of Coimbra, Coimbra, PortugalDepartment of Science and Environment, Roskilde University, Roskilde, DenmarkCenter for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; Institute for Interdisciplinary Research, University of Coimbra, Coimbra, PortugalCenter for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; Institute for Interdisciplinary Research, University of Coimbra, Coimbra, Portugal; Department of Geriatrics, University of Arkansas for Medical Sciences, and Arkansas Children’s Research Institute, Little Rock, AR, USADepartment of Science and Environment, Roskilde University, Roskilde, Denmark; Corresponding author: Håvard Jenssen, Department of Science and Environment, Roskilde University, Universitetsvej 1, 28A.2, 4000 Roskilde, Denmark.Bovine lactoferricin (LFcinB) has antimicrobial and immunomodulatory properties; however, the effects on diabetic wound healing remain poorly understood. The wound healing potential of LFcinB was investigated with in vitro, ex vivo, and in vivo models. Cell migration and proliferation were tested on keratinocytes and on porcine ears. A type 1 diabetic mouse model was also used to evaluate wound healing kinetics, bacterial diversity patterns, and the effect of LFcinB on oxidative stress, macrophage phenotype, angiogenesis, and collagen deposition. LFcinB increased keratinocyte migration in vitro (p < 0.05) and ex vivo (p < 0.001) and improved wound healing in diabetic mice (p < 0.05), though not in normoglycemic control mice. In diabetic mouse wounds, LFcinB treatment led to the eradication of Bacillus pumilus, a decrease in Staphylococcus aureus, and an increase in the Staphylococcus xylosus prevalence. LFcinB increased angiogenesis in diabetic mice (p < 0.01), but this was decreased in control mice (p < 0.05). LFcinB improved collagen deposition in both diabetic and control mice (p < 0.05). Both oxidative stress and the M1-to-M2 macrophage ratios were decreased in LFcinB-treated wounds of diabetic animals (p < 0.001 and p < 0.05, respectively) compared with saline, suggesting a downregulation of inflammation in diabetic wounds. In conclusion, LFcinB treatment demonstrated noticeable positive effects on diabetic wound healing.http://www.sciencedirect.com/science/article/pii/S2329050121000231bovine lactoferricinwound healingdiabetesimmunomodulationbacterial diversitymacrophage polarization |
| spellingShingle | Michelle V. Mouritzen Marija Petkovic Katrine Qvist Steen S. Poulsen Susana Alarico Ermelindo C. Leal Louise T. Dalgaard Nuno Empadinhas Eugenia Carvalho Håvard Jenssen Improved diabetic wound healing by LFcinB is associated with relevant changes in the skin immune response and microbiota Molecular Therapy: Methods & Clinical Development bovine lactoferricin wound healing diabetes immunomodulation bacterial diversity macrophage polarization |
| title | Improved diabetic wound healing by LFcinB is associated with relevant changes in the skin immune response and microbiota |
| title_full | Improved diabetic wound healing by LFcinB is associated with relevant changes in the skin immune response and microbiota |
| title_fullStr | Improved diabetic wound healing by LFcinB is associated with relevant changes in the skin immune response and microbiota |
| title_full_unstemmed | Improved diabetic wound healing by LFcinB is associated with relevant changes in the skin immune response and microbiota |
| title_short | Improved diabetic wound healing by LFcinB is associated with relevant changes in the skin immune response and microbiota |
| title_sort | improved diabetic wound healing by lfcinb is associated with relevant changes in the skin immune response and microbiota |
| topic | bovine lactoferricin wound healing diabetes immunomodulation bacterial diversity macrophage polarization |
| url | http://www.sciencedirect.com/science/article/pii/S2329050121000231 |
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