Perinatal high methyl donor alters gene expression in IGF system in male offspring without altering DNA methylation
FUTURE SCIENCE OA
Authors: Amarger, Valerie; Giudicelli, Fanny; Pagniez, Anthony; Parnet, Patricia
Abstract
Aim: To investigate the effect of a protein restriction and a supplementation with methyl donor nutrients during fetal and early postnatal life on the expression and epigenetic state of imprinted genes from the IGF system. Materials & methods: Pregnant female rats were fed a protein-restricted diet supplemented or not with methyl donor. Results: Gene expression of the Igf2, H19, Igf1, Igf2r and Plagl1 genes in the liver of male offspring at birth and weaning was strongly influenced by maternal diet. Whereas the methylation profiles of the Igf2, H19 and Igf2r genes were remarkably stable, DNA methylation of Plagl1 promoter was slightly modified. Conclusion: DNA methylation of most, but not all, imprinted gene regulatory regions was resistant to methyl group nutritional supply. Lay abstract: Fetal environment influences fetal growth and may confer a risk to develop metabolic diseases, possibly through alterations in the epigenetic state of the genome. Imprinted genes constitute a special class of genes that are crucial for the control of fetal and postnatal growth and are closely associated with energy metabolism. In addition, these genes are finely regulated by epigenetic mechanisms that are themselves influenced by environmental factors. This study showed that methyl donor nutrients in maternal diet strongly influenced the expression level of imprinted genes in the liver of rat offspring, despite a mild effect on epigenetic regulation.
Expression of small leucine-rich extracellular matrix proteoglycans biglycan and lumican reveals oral lichen planus malignant potential
CLINICAL ORAL INVESTIGATIONS
Authors: Loncar-Brzak, Bozana; Klobucar, Marko; Veliki-Dalic, Irena; Sabol, Ivan; Pavelic, Sandra Kraljevic; Kruslin, Bozo; Mravak-Stipetic, Marinka
Abstract
The aim of this study was to examine molecular alterations on the protein level in lesions of oral lichen planus (OLP), oral squamous cell carcinoma (OSCC) and healthy mucosa. Global protein profiling methods based on liquid chromatography coupled to mass spectrometry (LC-MS) were used, with a special emphasis on evaluation of deregulated extracellular matrix molecules expression, as well as on analyses of IG2F and IGFR2 expression in healthy mucosa, OLP and OSCC tissues by comparative semi-quantitative immunohistochemistry. Mass spectrometry-based proteomics profiling of healthy mucosa, OLP and OSCC tissues (and accompanied histologically unaltered tissues, respectively) identified 55 extracellular matrix proteins. Twenty among identified proteins were common to all groups of samples. Expression of small leucine-rich extracellular matrix proteoglycans lumican and biglycan was found both in OSCC and OLP and they were validated by Western blot analysis as putative biomarkers. A significant increase (p < 0.05) of biglycan expression in OLP-AT group was determined in comparison with OLP-T group, while lumican showed significant up-regulation (p < 0.05) in OLP-T and OSCC-T groups vs. adjacent and control tissue groups. Biglycan expression was only determined in OSCC-AT group. Immunohistochemical analysis of IGF2 and IG2FR expression revealed no significant difference among groups of samples. Biglycan and lumican were identified as important pathogenesis biomarkers of OLP that point to its malignant potential.