Hyperglycemia reduces integrin subunits alpha v and alpha 5 on the surface of dermal fibroblasts contributing to deficient migration

Autor(es)

Almeida, Maira Estanislau S. ; Monteiro, Kelly S. ; Kato, Ellen E. ; Sampaio, Sandra C. ; Braga, Tarcio T. ; Camara, Niels O. S. ; Lamers, Marcelo L. ; Santos, Marinilce F.

• Tipo de documento: Artigo Científico
• Fonte: Molecular and Cellular Biochemistry; v. 421, n. 1-2, p. 19-28, OCT 2016.
• Citações Web of Science: 9

Resumo

Deficient wound healing is a common multifactorial complication in diabetic patients, but the cellular and molecular mechanisms involved are poorly defined. In the present study, we analyzed the effects of hyperglycemia on integrins expression in rat dermal fibroblasts and addressed its role in cell adhesion and migration. Diabetes Mellitus was induced in rats by streptozotocin injection and maintained for 30 days. Primary cultures of dermal fibroblasts from control and diabetic rats were maintained under low glucose (5 mM d-glucose) or high glucose (30 mM d-glucose) for 7 days. Cell adhesion and migration were studied by kymography, transwell, and time-lapse assays, and the expressions of integrin subunits alpha v and alpha 5 were studied by immunocytochemistry and western blotting. Fibroblasts derived from diabetic rats confirmed a reduced migration speed and delayed spreading compared to fibroblasts derived from control rats. The membrane fraction of diabetic-derived fibroblasts showed a decrease of integrin subunits alpha 5 and alpha v, which was confirmed by immunocytochemistry assays. A reduction in the pericellular fibronectin matrix was also observed. The exposure of diabetic-derived cells to a higher concentration of exogenous fibronectin improved migration velocity and the expression of alpha v but did not completely restore their migration capacity. In conclusion, the mechanisms involved in the deleterious effects of Diabetes Mellitus on wound healing include the ability of fibroblasts to secrete and to adhere to fibronectin. (AU)

• Processo FAPESP: 12/15963-6 - Papel do estresse oxidativo e da glicação da matriz extracelular sobre a migração de fibroblastos dérmicos em diabéticos
• Beneficiário: Maíra Estanislau Soares de Almeida
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 12/03990-9 - Regulação da migração celular por microRNAs: implicações no Diabetes mellitus, regeneração tecidual e câncer
• Beneficiário: Marinilce Fagundes dos Santos
• Modalidade de apoio: Auxílio à Pesquisa - Regular