Evaluation of the involvement of the Ang II in the scaring process

• Grant number: 22/04521-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2022
• End date: August 31, 2024
• Field of knowledge: Biological Sciences - Pharmacology - Clinical Pharmacology
• Principal Investigator: Carlos Ferreira dos Santos
• Grantee: Marcelo Henrique Garcia
• Host Institution: Faculdade de Odontologia de Bauru (FOB). Universidade de São Paulo (USP). Bauru , SP, Brazil

Abstract

The study about the scarring process allowed the understanding of the molecular events that take place during wound healing. In this process, the local Renin Angiotensin System (RAS), present in the tissues, helps to balance the pro and anti-inflammatory response through bounding of Angiotensin (Ang) II to AT1 and AT2 receptors, and of Ang 1-7 to MAS receptor. In addition, some proteins such as TGF-²1, SMAD2 and 3, TAK1 and Collagen I may modulate wound healing. Thus, this project aims to evaluate the molecular aspects of wound healing of healthy, hypertensive and diabetic rats during the use of losartan, an angiotensin II AT1 receptor blocker. Therefore, healthy (n=12), hypertensive (n=12) and diabetic (n=12) rats will undergo a dorsal surgical incision for harvesting of a skin fragment. Losartan 50mg/kg/day will be administered by gavage for 30 days before surgery and for 15 more days after surgery. Swabs of surgical lesions after 24, 48 and 72 hours will be will be studied through mass spectrometry for the analysis of RAS peptides. Scar tissues will be used for identification of mRNA (qRT-PCR) for RAS components, TGF-²1, SMAD2 and 3, TAK1 and Collagen I. Also, histological analysis of the scar tissue will be performed for collagen deposition and macrophage characterization (M1 and M2). The results will be analyzed to verify the presence or absence of normal distribution in the groups (Shapiro-Wilk Test) and afterwards analyzed through an appropriate statistical test. The hypothesis of this study is the occurrence of scars with a better esthetic pattern in rats treated with losartan. (AU)