RESUMEN
Calcium (Ca2+) signaling has a major role in regulating a wide range of cellular mechanisms, including gene expression, proliferation, metabolism, cell death, muscle contraction, among others. Recent evidence suggests that ~ 1600 genes are related to the Ca2+ signaling. Some of these genes' expression is altered in several pathological conditions, including different cancer types, and epigenetic mechanisms are involved. However, their expression and regulation in hepatocellular carcinoma (HCC) and the liver are barely known. Here, we aimed to explore the expression of genes involved in the Ca2+-signaling in HCC, liver regeneration, and hepatocyte differentiation, and whether their expression is regulated by epigenetic mechanisms such as DNA methylation and histone posttranslational modifications (HPM). Results show that several Ca2+-signaling genes' expression is altered in HCC samples; among these, a subset of twenty-two correlate with patients' survival. DNA methylation correlates with eight of these genes' expression, and Guadecitabine, a hypomethylating agent, regulates the expression of seven down-regulated and three up-regulated genes in HepG2 cells. The down-regulated genes displayed a marked decrease of euchromatin histone marks, whereas up-regulated genes displayed gain in these marks. Additionally, the expression of these genes is modulated during liver regeneration and showed similar profiles between in vitro differentiated hepatocytes and liver-derived hepatocytes. In conclusion, some components of the Ca2+-signaling are altered in HCC and displayed a correlation with patients' survival. DNA methylation and HMP are an attractive target for future investigations to regulate their expression. Ca2+-signaling could be an important regulator of cell proliferation and differentiation in the liver.
RESUMEN
Gender differences in the immune response of insects are driven by natural selection for females and sexual selection for males. These natural forces entail a multitude of extrinsic and intrinsic factors involved in a genotype-environment interaction that results in sex-biased expression of the genes shared by males and females. However, little is known about how an infection at a particular ontogenetic stage may influence later stages, or how it may impact sexual immune dimorphism. Using Aedes aegypti mosquitoes, the aim of the present study was to analyze the effect of a bacterial exposure at the larval stage on adult immunity in males and females. The parameters measured were phenoloxidase activity, nitric oxide production, antimicrobial activity, and the antimicrobial peptide transcript response. As a measure of the immune response success, the persistence of injected bacteria was also evaluated. The results show that males, as well as females, were able to enhance survival in the adult stage as a result of being exposed at the larval stage, which indicates a priming effect. Moreover, there was a differential gender immune response, evidenced by higher PO activity in males as well as higher NO production and greater antimicrobial activity in females. The greater bacterial persistence in females suggests a gender-specific strategy for protection after a previous experience with an elicitor. Hence, this study provides a primary characterization of the complex and gender-specific immune response of male and female adults against a bacterial challenge in mosquitoes primed at an early ontogenetic stage.