Autor(es): Seraphim, Patricia M. [UNESP] ; Leal, Ermelindo C. ; Moura, João ; Gonçalves, Pedro ; Gonçalves, Jenifer P. ; Carvalho, Eugénia
Data: 2020
Identificador Persistente: http://hdl.handle.net/11449/200545
Origem: Oasisbr
Assunto(s): Diabetes; Inflammation; Lymphocytes; Reactive oxygen species; Wound healing; Diabetes; Diabetes; Inflammation; Inflammation; Lymphocytes; Lymphocytes; Reactive oxygen species; Reactive oxygen species; Wound healing; Wound healing
Made available in DSpace on 2020-12-12T02:09:27Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-08-01
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
AIMS: This study aimed to investigate the effect of lymphocytes in wound healing and the underlying mechanisms, in diabetic and non-diabetic mice, using Balb/c recombination activating gene (Rag)-2 and interleukin 2 receptor gamma (IL-2Rγ) double knockout (KO) (RAG2−/− IL-2Rγ−/−) mice. MAIN METHODS: Wound healing in vivo was performed in control and STZ-induced diabetic mice, in both KO and WT mice. Inflammation and ROS production were evaluated by immunofluorescence microscopy analysis, antioxidant enzymes and angiogenesis were evaluated by quantitative PCR and immunofluorescence microscopy analysis, and wound closure kinetics evolution was evaluated by measurement of acetate tracing of the wound area. KEY FINDINGS: Wound closure was significantly delayed in KO mice, where the M1/M2 macrophage ratio and basal ROS levels were significantly increased, while antioxidant defenses and angiogenesis were significantly decreased. Moreover, the expected increase in matrix metallopeptidase (MMP)-9 protein levels in diabetic conditions was not observed in KO mice, suggesting that the mechanisms leading to the increase in MMP-9 observed in diabetic wounds may in part be lymphocyte-dependent. SIGNIFICANCE: Our results indicate that lack of lymphocytes compromises wound healing independent of diabetes. The lack of these cells, even in non-diabetic mice, mimics the phenotype observed in wounds under diabetic conditions. Moreover, the combination of diabetes and the lack of lymphocytes, further impair the wound healing conditions, indicating that when the innate regulatory function is lost in these KO mice, excessive M1 polarization, poor angiogenesis and impaired wound healing are worsen.
Center for Neuroscience and Cell Biology University of Coimbra
Department of Physiotherapy School of Sciences and Technology Sao Paulo State University - UNESP, Campus Presidente Prudente
Instituto de Investigação Interdisciplinar University of Coimbra
Innate Immunity Unit Institut Pasteur
Institut National de la Santé et de la Recherche Médicale (INSERM) U1223
Cell Biology Department Federal University of Paraná
The Portuguese Diabetes Association (APDP)
Department of Geriatrics University of Arkansas for Medical Sciences
Arkansas Children's Research Institute
INEB - Instituto Nacional de Engenharia Biomédica University of Porto
i3S - Instituto de Investigação e Inovação em Saúde University of Porto
Department of Physiotherapy School of Sciences and Technology Sao Paulo State University - UNESP, Campus Presidente Prudente
CNPq: 203179/2011-0
CNPq: 233621/2014-8
