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EFFECT OF ANGIOTENSIN II AND ANGIOTENSIN-(1-7) IN PROLIFERATION OF STEM CELLS FROM HUMAN DENTAL APICAL PAPILLA
Dental papilla has been considered an important source of ectomesenchymal stem cells. Renin-angiotensin System (RAS) is a complex systemic cascade of interacting peptides and enzymes that coordinates a variety of physiological processes. This system has two main biologically active peptides, Ang II and Ang-(1-7). Previous studies have shown that these peptides can influence proliferation of progenitor cells. However, the role of RAS on the stem cells isolated from human dental apical papilla (SCAPs) is completely unknown.
Objetivos - Metodologia - Resultados - Discussão dos Resultados/Objectives - Methodology - Results - Discussion of Results/Objetivos - Metodología - Resultados - Discusión de los resultados
Thus, the aim of this study was to identify the presence of RAS components in SCAPs and the effects of the Ang II and Ang-(1-7) in the proliferation these cells. SCAPs were collected from third molar teeth of 12 healthy individuals aged 13-16 years. The primary culture was maintained in DMEM/F12 with 10% fetal bovine serum at 37°C and in 5% CO2. RT-PCR and Western Blotting was used to identify the mRNA and protein expression of the Angiotensin-converting Enzyme (ACE), ACE2, Mas, AT1 and AT2 receptors. Carboxyfluorescein succinimidyl ester (CFSE) assay was used to evaluate the effect of the Ang II and Ang-(1-7) in the cell proliferation. SCAPs were plated at 5x105 cells/mL for 8 h and incubated with Ang II (10-8 to 10-5 mol/L) or Ang-(1-7) (10-8 to 10-5 mol/L) in presence or absence of Losartan (AT1 receptor antagonist, 10-6 mol/L), PD12319 (AT2 receptor antagonist, 10-6 mol/L) or A-779 (Mas receptor antagonist, 10-6 mol/L). Western Blotting was also used to identify the signaling pathways involved in the proliferative effects of the peptides. mRNA expression and protein levels of ACE, ACE2, and AT1, AT2 and Mas receptors were detected in SCAPs. Both Ang II and Ang-(1-7) increased the stem cell proliferation. These effects were inhibited by PD123319. Ang II decreased total mTOR expression and augmented mTOR phosphorylation. Ang-(1-7) diminished total mTOR, p-AKT and p-GSK-3 beta expression, and increased ERK1/2 phosphorylation.
Considerações Finais/Final considerations/Consideraciones finales
In conclusion, SCAPs present the main RAS components and both Ang II and Ang-(1-7) treatments induced cell proliferation mediated by AT2 activation. However, while Ang II induced stem cell proliferation through mTOR activation, Ang-(17) stimulated proliferation in an AKT/mTOR and ERK1/2-dependent manner.
Palavras-chave/Key words/Palabras clave
RAS, SCAPs, Ang II, Ang-(1-7), AT2, stem cell proliferation, Carboxyfluorescein succinimidyl assay, CFSE, AKT, mTOR, GSK3 beta, ERK1/2.
Mesenchymal stem cells/adultas
LARISSA MATUDA MACEDO, Renato Ivan Ávila, Marize Campos Valadares, Eliana Martins Lima, Clayton Luiz Borges, Elisandra Gava, Carlos Henrique de Castro