Mechanisms involved in the effects of linoleic fatty acid on wound healing in diabetic mice: focus on the inflammatory and angiogenesis response

Author(s)

Jéssica Rondoni Silva Fernandes

• Document type: Doctoral Thesis
• Press: Limeira, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Aplicadas
• Defense date: 2023-01-31

Examining board members

Hosana Gomes Rodrigues; Adriana Souza Torsoni; Fernando Moreira Simabuco; Alexandra Ivo de Medeiros

• Advisor: Hosana Gomes Rodrigues

Abstract

Based on the literature, it is known that the oral administration of fatty linoleic acid (LA) improves different stages of tissue repair under normal conditions. However, little is known about its effects in the treatment of wounds in diabetics. The uncontrolled increase in blood glucose, the exacerbation and chronicity of the inflammatory response are factors that contribute to the delayed healing of diabetic wounds. Since inflammation is the first of the 3 phases that occur in the wound healing process, it is vitally important to pay attention to therapies that accelerate this phase, thus bringing a quick resolution of the wound. Thus, this study aimed to evaluate the effects of oral administration of linoleic acid on wound healing in mice submitted to type I diabetes (DM) (Ethics Committee: 5466-1/2020). For this purpose, male C57black/6 mice were divided into three groups: (C) control; (D) diabetic animals induced by streptozotocin and (DLA) diabetic animals supplemented with linoleic acid. We analyzed: nutritional parameters, serum and feed lipid composition, wound closure, skin mechanical properties assay, microscopic analysis of undamaged skin, cytokine and growth factors production, immunophenotyping, angiogenesis PCR array. Based on our results, we saw that LA supplementation did not change nutritional parameters compared to group D, showing that the observed differences were due to supplementation only, and not changes caused by nutritional status. We also saw that oral administration of LA accelerated wound closure as well as being able to modulate the incorporation of fatty acids into the serum and altering the skin's elastic properties. PCRarray analyzes suggest that in the DLA group there was modulation of pathways involved in migration, proliferation, angiogenesis and growth factor signaling. Based on flow cytometry, we saw that DLA decreased the neutrophil population 1 day after injury, in relation to the diabetic group, and in addition, it modulated the expression of CXCL1. Together these results suggest that at the CXCL1 pathway may be one of those responsible for the restore of wound closure on diabetic supplemented animals. We conclude that the supplementation of diabetic animals with LA accelerates wound closure by mechanisms that seems to depend on CXCL1 pathway with neutrophils activation and e its consequently functions as a modulator of inflammatory phase of wound healing process in diabetic animals (AU)

• FAPESP's process: 19/00596-7 - Mechanisms of action involved in the effects of LA on wound healing in diabetic mice: focus on inflammatory response and angiogenesis
• Grantee: Jessica Rondoni Silva
• Support Opportunities: Scholarships in Brazil - Doctorate