ROLE OF OXIDATIVE STRESS AND EXTRACELLULAR MATRIX GLYCATION ON MIGRATION OF DIABETIC SKIN FIBROBLASTS

• Grant number: 12/15963-6
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: November 01, 2012
• End date: September 30, 2015
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Marinilce Fagundes dos Santos
• Grantee: Maíra Estanislau Soares de Almeida
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Diabetes Mellitus (DM) is a metabolic disease characterized by chronic hyperglycemia, which damages different cells and tissues. A common long term complication of DM is wound healing impairment, a problem that significantly reduces life quality for the patients. The main mechanisms involved in DM complications are oxidative stress and extracellular matrix (ECM) protein glycation. Glycation is aleatory and may affect intracellular as well as extracellular proteins. Considering the long half-life of ECM proteins, it is possible that cumulative glycation may affect cell function. Few studies have evaluated the role of hyperglycemia-derived ECM glycation and oxidative stress on fibroblast functions, especially on their migratory activity. Studies from this group showed that hyperglycemia negatively affects fibroblast migration on bidimensional (2-D) substrates, reducing cell velocity and directionality (Lamers et al., 2011; Almeida, 2011). The same observation was true for tridimensional (3-D) substrates. Preliminary results suggest that diabetic cells may have deficient myosin II activity, which might be critical for adhesion maturation and 3-D cell migration (Almeida, 2011). It is possible that this impaired migration might be even worse in the presence of glycated ECM, a situation observed in vivo in diabetic patients. The aim of this study is to evaluate the role of oxidative stress and ECM glycation on cell contractility, particularly on myosin II isoforms A and B, and their influence on the migration of normoglycemic and hyperglycemic skin fibroblasts.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

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.. Hyperglycemia reduces integrin subunits alpha v and alpha 5 on the surface of dermal fibroblasts contributing to deficient migration. Molecular and Cellular Biochemistry, v. 421, n. 1-2, p. 19-28, OCT 2016. (12/15963-6, 12/03990-9)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

ALMEIDA, Maíra Estanislau Soares de. Roles of collagen I glycation and high glucose concentration on fibroblast migration.. 2015. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.