Mechanisms of action involved in the effects of LA on wound healing in diabetic mice: focus on inflammatory response and angiogenesis

• Grant number: 19/00596-7
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): December 01, 2019
• Effective date (End): November 30, 2022
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal Investigator: Hosana Gomes Rodrigues
• Grantee: Jessica Rondoni Silva
• Host Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil

Abstract

Delay in wound healing affects millions of people worldwide, especially Diabetic individuals. It has been shown in the literature, both in laboratory animal studies and clinical trials, that oral administration of linoleic fatty acid (LA) improves different stages of tissue repair under normal conditions. Thus, in the present work, we intend to investigate the effects of oral supplementation with LA fatty acid on inflammatory response and blood vessel formation during wound healing in Diabetic mice. For diabetes induction, we will use a protocol of 5 consecutive doses of streptozotocin (45mg / kg body weight). After diabetes confirmation, the animals will be orally supplemented with pure LA (50¼L) during 5 days. Then, we will induce the wounds on the backs of the animals and the scar tissues will be collected for analysis. To evaluate the effects of LA on the inflammatory response we will use animal knockouts for the tumor necrosis factor receptor (TNFR -/-). In these animals we will evaluate the production of inflammatory mediators, as well as the cell types present in the skin during wound healing. To investigate the effects of LA on angiogenesis, we will use reporter animals for the VE-cadherin cell junction protein (VECaderinCre + Tomato +) and animals HIF-1± specific tissue knockouts only in endothelial cells (VECaderinCre + Tomato + HIF-1floxed). In these animals we will evaluate the expression of genes involved with angiogenesis through PCR array; we will analyze the phosphorylation status of key proteins for angiogenesis based on PCRarray results; we will evaluate vessel formation during the healing process by tissue flow cytometry; and investigate the angiogenesis steps in skin-derived organoids. (AU)