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Doctoral Thesis
DOI
https://doi.org/10.11606/T.42.2008.tde-11112008-131435
Document
Author
Full name
Marcelo Lazzaron Lamers
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2008
Supervisor
Committee
Santos, Marinilce Fagundes dos (President)
Larson, Roy Edward
Moraes, Flavio Fava de
Nicolau, Jose
Nunes, Fabio Daumas
Title in Portuguese
Concentração elevada de glicose e interação célula-matriz extracelular: efeitos sobre a homeostase de glândulas salivares, adesão e migração celular.
Keywords in Portuguese
Diabetes
Estresse oxidativo
Glândula salivar
Matriz extracelular
Migração celular
TGFb
Abstract in Portuguese
Neste estudo avaliou-se os efeitos do diabetes mellitus (DM) sobre dois sistemas: glândula parótida de ratos e células cultivadas in vitro. Foram avaliados respectivamente a composição da matriz extracelular e a migração de células expostas a elevada concentração de glicose. Na parótida observou-se aumento de colágenos III, IV e V, laminina e fibronectina, mediado por TGFb2. Em células isoladas observou-se que a glicose dificultou a polarização celular, reduziu a velocidade e direcionalidade de migração, reduziu a persistência e estabilidade das protrusões celulares e a maturação de adesões. Estas alterações estão relacionadas à ativação da GTPase Rac1, dependente de estresse oxidativo. Este estudo sugere, pela primeira vez, que: 1) a hipofunção salivar pode envolver um espessamento da lâmina basal de capilares e parênquima por mecanismos previamente observados em outros orgãos-alvo de complicações diabéticas e 2) que a glicose exerce um efeito direto sobre a migração celular, fator que pode contribuir para a cicatrização deficiente em indivíduos diabéticos.
Title in English
High glucose concentration and cell-extracellular matrix interaction: effects on salivary gland homeostasis, cell adhesion and migration.
Keywords in English
Cell migration
Diabetes
Extracellular matrix
Oxidative stress
Salivary gland
TGFb
Abstract in English
In this study we evaluated the effects of DM on two different systems: the rat parotid gland and in vitro cultured cells. Extracellular matrix composition and the migratory behavior of cells exposed to a high glucose concentration (HG) were evaluated, respectively. In the parotid, DM led to an increase in collagens III, IV and V, laminin and fibronectin, through a TGFb2-dependent mechanism. In cultured cells, HG impaired cell polarization, reduced migration velocity and directionality, reduced the persistence and stability of protrusive cellular processes, as well as adhesion maturation. These effects were related to Rac1 GTPase activation, dependent on the oxidative stress promoted by HG. This study suggests, for the first time, that: 1) salivary hypofunction in DM might involve the thickening of capillary and parenchyma basal lamina, through mechanisms already described in other target organs for diabetic complications and 2) that glucose directly impairs cell migration, and this effect may contribute to the chronic wound healing observed in diabetic patients.
 
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Publishing Date
2008-11-12
 
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