The role the receptor PPAR alpha in wound healing induced experimentally

Author(s)

Francielle Rodrigues Guimarães

• Document type: Master's Dissertation
• Press: Ribeirão Preto.
• Institution: Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto (PCARP/BC)
• Defense date: 2013-04-12

Examining board members

Cristina Ribeiro de Barros Cardoso; Jayme Adriano Farina Junior; Fabiani Gai Frantz

• Advisor: Cristina Ribeiro de Barros Cardoso

Abstract

Peroxissome proliferator-activated receptor alpha (PPAR?) is a nuclear transcription factor involved in the regulation of lipid metabolism and inflammation. PPAR? may be associated to the modulation of wound healing, which is a multifactorial process dependent on mechanisms of cell signaling and inflammation. Then this work aimed to analyze the role of PPAR? receptor in experimental cutaneous wound healing and its relationship to the systemic metabolism of mice treated with a PPAR? agonist. For this, skin wounds were performed in the dorsal region of 129/SvEv mice, treated daily with the PPAR? agonist, Gemfibrozil, by oral or topical route. Mice were followed for 240h post-surgery (p.s.) for skin repair and metabolic changes that could be induced by PPAR? activation. There was improved wound healing in mice treated with 100 or 50 mg/Kg of PPAR? agonist by oral or topical route respectively. The oral treatment induced a better repair in the early 24h, 48h and 72h p.s. while mice treated by topical application of Gemfibrozil presented faster healing in all times evaluated. Wound\'s induction affected the systemic metabolism of mice leading to significant weight loss. PPAR? agonist did not alter glucose, triglycerides or liver function, although all injured animals had a significant decrease on triglycerides levels in the early times p.s., independent on the treatment. In histopathological examination of the wounds it was observed inflammatory infiltrate, composed mainly of neutrophils and other polymorphonuclear cells. However, topical treatment with PPAR? agonist led to lower inflammatory infiltrate and differentiated collagen deposition 10 days p.s. Furthermore, there was decrease of neutrophil, macrophages and eosinophils influx when compared to untreated mice. Topical treatment led to decrease in the TCD4+, TCD8+ e T?? lymphocytes accumulation in the lesions, and differentiated dendritic cell influx to the wounds. However there was no difference regarding CD4+CD25+ T cells in lymph nodes, but treated mice showed decrease Foxp3 expression. In conclusion, the triglycerides serum level was altered in the course of wound healing and may be associated to skin lesion, while PPAR? agonist acts in wound repair by accelerating healing and modulating neutrophil influx to the skin. Finally, our results suggested that PPAR? may be an important target for novel therapies aimed at improved wound healing, especially when administered topically. (AU)

• FAPESP's process: 11/02718-0 - The role of PPAR alpha receptor in experimental cutaneous wound healing
• Grantee: Francielle Rodrigues Guimarães
• Support Opportunities: Scholarships in Brazil - Master