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Title: Improved diabetic wound healing by LFcinB is associated with relevant changes in the skin immune response and microbiota
Authors: Mouritzen, Michelle V.
Petkovic, Marija 
Qvist, Katrine
Poulsen, Steen S.
Alarico, Susana 
Leal, Ermelindo C. 
Dalgaard, Louise T.
Empadinhas, Nuno 
Carvalho, Eugenia 
Jenssen, Håvard
Keywords: bacterial diversity; bovine lactoferricin; collagen deposition; diabetes; immunomodulation; inflammatory cytokines; macrophage polarization; wound healing
Issue Date: 12-Mar-2021
Publisher: Elsevier
Project: Danish Council for Independent Research, Technology and Production (grant 4005-00029). 
Lundbeck R275-2017- 2793 and Erasmus+ F2: 2015-5577 
POCI- 01-0145-FEDER-007440 
Healthy Aging 2020- CENTRO-01-0145-FEDER-000012-N2323 
DL57/2016/CP1448/ CT0024 
NIGMS P20GM109096 
EFSD European Research Programme in Microvascular Complications/Novartis Pharma AG 
Infarmed grant FIS-FIS- 2015-01_DIA_20150630-144 
Serial title, monograph or event: Molecular Therapy - Methods and Clinical Development
Volume: 20
Abstract: 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.
ISSN: 2329-0501
DOI: 10.1016/j.omtm.2021.02.008
Rights: openAccess
Appears in Collections:I&D CNC - Artigos em Revistas Internacionais
IIIUC - Artigos em Revistas Internacionais

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