New Peroxisome Proliferator-Activated Receptor Agonist (GQ-11) Improves Wound Healing in Diabetic Mice

Autor(es)

Silva, Jacqueline C. ^[1] ; Pitta, Marina G. R. ^[2] ; Pitta, Ivan R. ^[2] ; Koh, Timothy J. ^[3] ; Abdalla, Dulcineia S. P. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Pharmaceut Sci, Dept Clin & Toxicol Anal, Ave Prof Lineu Prestes 580, BR-05508000 Sao Paulo, SP - Brazil

^[2] Univ Fed Pernambuco, Ctr Biol Sci, Core Therapeut Innovat, Recife, PE - Brazil

^[3] Univ Illinois, Coll Appl Hlth Sci, Dept Kinesiol & Nutr, 1919 West Taylor St, 529 AHSB, Chicago, IL 60612 - USA

• Tipo de documento: Artigo Científico
• Fonte: ADVANCES IN WOUND CARE; v. 8, n. 9, p. 417-428, SEP 1 2019.
• Citações Web of Science: 0

Resumo

Objective: Chronic wounds associated with diabetes are an important public health problem demanding new treatments to improve wound healing and decrease amputations. Monocytes/macrophages play a key role in sustained inflammation associated with impaired healing and local administration of peroxisome proliferator-activated receptor (PPAR)gamma agonists may modulate macrophage, improving healing. In this study, we investigated the effects of GQ-11, a partial/dual PPAR alpha/gamma agonist, on macrophage function and wound healing in diabetes. Approach: Wounds were surgically induced at the dorsum of C57BL/6J and BKS.Cg-Dock7(m) +/+ Lepr(db)/J (db/db) mice and treated with hydrogel (vehicle), pioglitazone or GQ-11, for 7 or 10 days, respectively. After treatment, wounds were analyzed histologically and by quantitative PCR (qPCR). In addition, bone marrow-derived macrophages (BMDM) were cultured from C57BL/6J mice and treated with vehicle, pioglitazone, or GQ-11, after challenge with lipopolysaccharide or interleukin-4 to be analyzed by qPCR and flow cytometry. Results: GQ-11 treatment upregulated anti-inflammatory/pro-healing factors and downregulated pro-inflammatory factors both in wounds of db/db mice and in BMDM. Innovation: Wounds of db/db mice treated with GQ-11 exhibited faster wound closure and re-epithelization, increased collagen deposition, and less Mac-3 staining compared with vehicle, providing a new approach to treatment of diabetic wound healing to prevent complications. Conclusion: GQ-11 improves wound healing in db/db mice, regulating the expression of pro- and anti-inflammatory cytokines and wound growth factors, leading to increased re-epithelization and collagen deposition. (AU)

• Processo FAPESP: 12/51316-5 - Investigação da atividade de biofármacos, agonistas de PPARs e produtos naturais com potencial terapêutico na aterosclerose
• Beneficiário: Dulcineia Saes Parra Abdalla
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 16/00233-3 - "Ação de um novo derivado tiazolidínico (GQ-11) no processo de reparo tecidual em modelo experimental de resistência a insulina e cirurgia vascular".
• Beneficiário: Jacqueline Cavalcante Silva
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 16/16850-1 - Ação de um novo derivado tiazolidínico (GQ-11) no processo de reparo tecidual em modelo experimental de resistência à insulina e isquemia
• Beneficiário: Jacqueline Cavalcante Silva
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado