Induction of Epithelial Mesenchimal Transition and Vasculogenesis in the Lenses of Dbl Oncogene Transgenic Mice

BACKGROUND: The Dbl family of proteins represents a large group of proto-oncogenes involved in cell growth regulation. The numerous domains that are present in many Dbl family proteins suggest that they act to integrate multiple inputs in complicated signaling networks involving the Rho GTPases. Alterations of the normal function of these proteins lead to pathological processes such as developmental disorders and neoplastic transformation. We generated transgenic mice introducing the cDNA of Dbl oncogene linked to the metallothionein promoter into the germ line of FVB mice and found that onco-Dbl expression in mouse lenses affected proliferation, migration and differentiation of lens epithelial cells. RESULTS: We used high density oligonucleotide microarray to define the transcriptional profile induced by Dbl in the lenses of 2 days, 2 weeks, and 6 weeks old transgenic mice. We observed modulation of genes encoding proteins promoting epithelial-mesenchymal transition (EMT), such as down-regulation of epithelial cell markers and up-regulation of fibroblast markers. Genes encoding proteins involved in the positive regulation of apoptosis were markedly down regulated while anti-apoptotic genes were strongly up-regulated. Finally, several genes encoding proteins involved in the process of angiogenesis were up-regulated. These observations were validated by histological and immunohistochemical examination of the transgenic lenses where vascularization can be readily observed. CONCLUSION: Onco-Dbl expression in mouse lens correlated with modulation of genes involved in the regulation of EMT, apoptosis and vasculogenesis leading to disruption of the lens architecture, epithelial cell proliferation, and aberrant angiogenesis. We conclude that onco-Dbl has a potentially important, previously unreported, capacity to dramatically alter epithelial cell migration, replication, polarization and differentiation and to induce vascularization of an epithelial tissue

Analysis of Roughness and Surface Hardness of a Dental Composite Using Atomic Force Microscopy and Microhardness Testing

The objective of this study was to evaluate the influence of a cola soft drink (CSD) and coffee on the microhardness and surface roughness of composite resin. Fifty cavities were prepared on the vestibular surface of bovine incisors and restored with nanoparticulate resin. The teeth were divided into five groups (n = 10): group A (control), immersion in artificial saliva (AS) for 14 days; group B, immersion in coffee for 15 min (3x/day) for 7 days followed by immersion in AS for another 7 days; group C, immersion in CSD for 15 min (3x/day) for 7 days followed by immersion in AS for another 7 days; group D, immersion in AS for 7 days, immersion in coffee for 15 min (3x/day) for 7 days; group E, immersion in AS for 7 days, immersion in CSD for 15 min (3x/day) for 7 days. After the immersion periods the specimens were analyzed for their microhardness and surface roughness. The data were subjected to analysis of variance (ANOVA) followed by t-test with 5% significance. Group A presented the highest average microhardness and lowest surface roughness, so it was possible to conclude that the consumption of CSD and coffee alters the microhardness and surface roughness of new restorations.o TEXTO COMPLETO DESTE ARTIGO, ESTARÁ DISPONÍVEL À PARTIR DE AGOSTO DE 2015.173446451Brazilian institutions Fundacao de Amparo a Pesquisa do Estado de Alagoa